Review written for clinicians and mammalian researchers about non-mammalian models of epilepsy

Cunliffe VT, Baines RA, Giachello CN, Lin WH, Morgan A, Reuber M, Russell C, Walker MC, Williams RS. Epilepsy research methods update: Understanding the causes of epileptic seizures and identifying new treatments using non-mammalian model organisms. Seizure. 2014 Oct 13. PMID: 25457452.

From the abstract:  "This narrative review is intended to introduce clinicians treating epilepsy and researchers familiar with mammalian models of epilepsy to experimentally tractable, non-mammalian research models used in epilepsy research, ranging from unicellular eukaryotes to more complex multicellular organisms. The review focuses on four model organisms: the social amoeba Dictyostelium discoideum, the roundworm Caenorhabditis elegans, the fruit fly Drosophila melanogaster and the zebrafish Danio rerio. ..."

Drosophila model of triosephosphate isomerase (TPI) deficiency

Roland BP, Amrich CG, Kammerer CJ, Stuchul KA, Larsen SB, Rode S, Aslam AA, Heroux A, Wetzel R, VanDemark AP, Palladino MJ. Triosephosphate isomerase I170V alters catalytic site, enhances stability and induces pathology in a Drosophila model of TPI deficiency. Biochim Biophys Acta. 2015 Jan;1852(1):61-9. PMID: 25463631.

Neurodegenerative models--catching up

Catching up on recent papers related to Drosophila as a model for neurodegenerative diseases.

Fernandes AC, Uytterhoeven V, Kuenen S, Wang YC, Slabbaert JR, Swerts J, Kasprowicz J, Aerts S, Verstreken P. Reduced synaptic vesicle protein degradation at lysosomes curbs TBC1D24/sky-induced neurodegeneration. J Cell Biol. 2014 Nov 24;207(4):453-62. PMID: 25422373; PMCID: PMC4242831. From the abstract: "In this paper, we study Drosophila melanogaster lacking active TBC1D24/Skywalker (Sky), a protein that in humans causes severe neurodegeneration, epilepsy, and DOOR (deafness, onychdystrophy, osteodystrophy, and mental retardation) syndrome, ... Using chimeric fluorescent timers, we show that synaptic vesicle-associated proteins were younger on average ... Using a genetic screen, we find that reducing endosomal-to-lysosomal trafficking ... rescued the neurotransmission and neurodegeneration defects in sky mutants. ... Our findings define a mechanism in which synaptic transmission is facilitated by efficient protein turnover at lysosomes and identify a potential strategy to suppress defects arising from TBC1D24 mutations in humans. "

Vanden Broeck L, Kleinberger G, Chapuis J, Gistelinck M, Amouyel P, Van Broeckhoven C, Lambert JC, Callaerts P, Dermaut B. Functional complementation in Drosophila to predict the pathogenicity of TARDBP variants: evidence for a loss-of-function mechanism. Neurobiol Aging. 2014 Sep 28. pii: S0197-4580(14)00596-X. PMID: 25442115.

Jäckel S, Summerer AK, Thömmes CM, Pan X, Voigt A, Schulz JB, Rasse TM, Dormann D, Haass C, Kahle PJ. Nuclear import factor transportin and arginine methyltransferase 1 modify FUS neurotoxicity in Drosophila. Neurobiol Dis. 2014 Nov 8;74C:76-88. PMID: 25447237. From the abstract: "... To investigate the requirements for the nuclear import of FUS in an in vivo model, we generated different transgenic Drosophila lines expressing human FUS wild type (hFUS wt) and two disease-related variants P525L and R495X, in which the NLS is mutated or completely absent, respectively. ..."

Pogson JH, Ivatt RM, Sanchez-Martinez A, Tufi R, Wilson E, Mortiboys H, Whitworth AJ. The Complex I Subunit NDUFA10 Selectively Rescues Drosophila pink1 Mutants through a Mechanism Independent of Mitophagy. PLoS Genet. 2014 Nov 20;10(11):e1004815. doi: 10.1371/journal.pgen.1004815. PMID: 25412178; PMCID: PMC4238976.

Jahromi SR, Haddadi M, Shivanandappa T, Ramesh SR. Modulatory effect of Decalepis hamiltonii on ethanol-induced toxicity in transgenic Drosophila model of Parkinson's disease. Neurochem Int. 2014 Nov 5;80C:1-6. doi: PMID: 25451756.

Siddique YH, Faisal M, Naz F, Jyoti S, Rahul. Role of Ocimum sanctum leaf extract on dietary supplementation in the transgenic Drosophila model of Parkinson's disease. Chin J Nat Med. 2014 Oct;12(10):777-81. PMID: 25443371.

Could custom fly cell lines help your disease model-related research? See post at FlyRNAi.

FlyRNAi: Thinking ahead--What could custom CRISPR engineere...: Open call to the Drosophila research community from the DRSC : Since it was founded in 2003 by Prof. N. Perrimon, the Drosophila RNAi Sc...

Nedd4 in fly and rodent models of Parkinson's disease

Davies SE, Hallett PJ, Moens T, Smith G, Mangano E, Kim HT, Goldberg AL, Liu JL, Isacson O, Tofaris GK. Enhanced ubiquitin-dependent degradation by Nedd4 protects against α-synuclein accumulation and toxicity in animal models of Parkinson's disease. Neurobiol Dis. 2014 Apr;64:79-87. PMID: 24388974; PMCID: PMC3988924.

From the abstract: "... Here we asked whether Nedd4-mediated degradation protects against α-synuclein-induced toxicity in the Drosophila and rodent models of Parkinson's disease. We show that overexpression of Nedd4 can rescue the degenerative phenotype from ectopic expression of α-synuclein in the Drosophila eye. ..."

Several recent reports--fly models of neurodegenerative diseases

Phom L, Achumi B, Alone DP, Muralidhara M, Yenisetti SC. Curcumin's Neuroprotective Efficacy in Drosophila Model of Idiopathic Parkinson's Disease is Phase Specific: Implication of its Therapeutic Effectiveness. Rejuvenation Res. 2014 Sep 19. PMID: 25238331.

Mizielinska S, Grönke S, Niccoli T, Ridler CE, Clayton EL, Devoy A, Moens T, Norona FE, Woollacott IO, Pietrzyk J, Cleverley K, Nicoll AJ, Pickering-Brown S, Dols J, Cabecinha M, Hendrich O, Fratta P, Fisher EM, Partridge L, Isaacs AM. C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins. Science. 2014 Sep 5;345(6201):1192-4. PMID: 25103406.

Latypova EM, Timoshenko SI, Kislik GA, Vitek MP, Schwarzman AL, Sarantseva SV. [Investigation of neuroprotective activity of apolipoprotein E peptide mimetic Cog1410 in transgenic lines of drosophila melanogaster.]. Biomed Khim. 2014 Jul;60(4):515-521. [article in Russian.] PMID: 25249536.

Liao J, Morin LW, Ahmad ST. Methods to Characterize Spontaneous and Startle-induced Locomotion in a Rotenone-induced Parkinson's Disease Model of Drosophila. J Vis Exp. 2014 Aug 17;(90). PMID: 25178101.

Buhlman L, Damiano M, Bertolin G, Ferrando-Miguel R, Lombès A, Brice A, Corti O. Functional interplay between Parkin and Drp1 in mitochondrial fission and clearance. Biochim Biophys Acta. 2014 Sep;1843(9):2012-26. PMID: 24878071.

Marcora MS, Fernández-Gamba AC, Avendaño LA, Rotondaro C, Podhajcer OL, Vidal R, Morelli L, Ceriani MF, Castaño EM. Amyloid peptides ABri and ADan show differential neurotoxicity in transgenic Drosophila models of familial British and Danish dementia. Mol Neurodegener. 2014 Jan 9;9:5. PMID: 24405716; PMCID: PMC3898387.  From the abstract: "Familial British and Familial Danish dementias (FBD and FDD, respectively) are associated with mutations in the BRI2 gene. ... In this work we have modeled FBD and FDD in Drosophila and tested the hypothesis that ABri and ADan are differentially neurotoxic."

Flies used in a study related to Lambert-Eaton Myasthenic Syndrome and Nonprogressive Motor Neuropathy

Herrmann DN, Horvath R, Sowden JE, Gonzales M, Sanchez-Mejias A, Guan Z, Whittaker RG, Almodovar JL, Lane M, Bansagi B, Pyle A, Boczonadi V, Lochmüller H, Griffin H, Chinnery PF, Lloyd TE, Littleton JT, Zuchner S. Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy. Am J Hum Genet. 2014 Sep 4;95(3):332-9. PMID: 25192047; PMCID: PMC4157148.

From the abstract: "... Characterization of the mutation homologous to the human c.920A>C variant in Drosophila Synaptotagmin revealed a dominant disruption of synaptic vesicle exocytosis using this transgenic model. ..."

'Spliceosensor' in flies for high-throughput screening related to myotonic dystrophy

García-Alcover I, Colonques-Bellmunt J, Garijo R, Tormo JR, Artero R, Alvarez-Abril MC, López Castel A, Pérez Alonso M. Development of a Drosophila melanogaster spliceosensor system for in vivo high-throughput screening in myotonic dystrophy type 1. Dis Model Mech. 2014 Sep 19. pii: dmm.016592. PMID: 25239918.

From the abstract: "... This powerful Drosophila-based screening tool might also be applied in other  disease models displaying abnormal alternative splicing, thus offering myriad uses in drug discovery."

Review--insights from fly and mouse models of Fragile X

Santos AR, Kanellopoulos AK, Bagni C. Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: what a fly and mouse model can teach us. Learn Mem. 2014 Sep 16;21(10):543-555. PMID: 25227249.

Impaired GABAergic circuit structure and function reported for fly model of Fragile-X syndrome

Gatto CL, Pereira D, Broadie K. GABAergic circuit dysfunction in the Drosophila Fragile X syndrome model. Neurobiol Dis. 2014 May;65:142-59. PMID: 24423648; PMCID: PMC3988906.

Fly model of Alzheimer's disease--Finding what's not?

Lüchtenborg AM, Katanaev VL. Lack of evidence of the interaction of the Aß peptide with the Wnt signaling cascade in Drosophila models of Alzheimer's disease. Mol Brain. 2014 Nov 12;7(1):81. PMID: 25387847.

From the abstract: "... Our data confirm that the life span is a useful readout of Aß42 induced neurotoxicity in Drosophila; the neuromuscular junction seems however not to be an appropriate model to study AD in flies. Additionally, our results challenge the hypothesis that Wnt signaling might be implicated in Aß42 toxicity and might serve as a drug target against AD."

Review--neurotransmitter release in mammals and flies--relevance to neurodegenerative disease

Davis GW, Müller M. Homeostatic Control of Presynaptic Neurotransmitter Release. Annu Rev Physiol. 2014 Nov 5. PMID: 25386989.

From the abstract: "This review focuses on the homeostatic modulation of presynaptic neurotransmitter release ... we highlight criteria that can be used to define a process as being under homeostatic control. Next, we review the remarkable conservation of presynaptic homeostasis at the Drosophila, mouse, and human neuromuscular junctions ... We then highlight recent progress identifying cellular and molecular mechanisms. We conclude by reviewing emerging parallels between the mechanisms of homeostatic signaling and genetic links to neurological disease."

Drosophila accessory gland as system for study of prostate cancer

Ito S, Ueda T, Ueno A, Nakagawa H, Taniguchi H, Kayukawa N, Miki T. A genetic screen in Drosophila for regulators of human prostate cancer progression. Biochem Biophys Res Commun. 2014 Sep 5;451(4):548-55. PMID: 25117438.

From the abstract: "... identified three genes that promoted growth and migration of secondary cells in the accessory gland. The human homologues of these candidate genes - MRGBP, CNPY2, and MEP1A - were found to be expressed in human prostate cancer model cells and to promote replication and invasiveness in these cells."

Fly study suggests a link between Huntingtin protein and autophagy

Ochaba J, Lukacsovich T, Csikos G, Zheng S, Margulis J, Salazar L, Mao K, Lau AL, Yeung SY, Humbert S, Saudou F, Klionsky DJ, Finkbeiner S, Zeitlin SO, Marsh JL, Housman DE, Thompson LM, Steffan JS. Potential function for the Huntingtin protein as a scaffold for selective autophagy. Proc Natl Acad Sci U S A. 2014 Nov 10. pii: 201420103. PMID: 25385587.

Review--Myosin in model systems and links to disease

Lee CF, Melkani GC, Bernstein SI. The UNC-45 Myosin Chaperone: From Worms to Flies to Vertebrates. Int Rev Cell Mol Biol. 2014;313:103-44. PMID: 25376491.

From the abstract: "UNC-45 (uncoordinated mutant number 45) is a UCS (UNC-45, CRO1, She4p) domain protein that is critical for myosin stability and function. It likely aides in folding myosin during cellular differentiation and maintenance, and protects myosin from denaturation during stress. ... we provide insights into UNC-45 functions, its potential mechanism of action, and its roles in human disease."

FlyRNAi: in vivo RNAi screen related to ALS

FlyRNAi: in vivo RNAi screen related to ALS: Deivasigamani S, Verma HK, Ueda R, Ratnaparkhi A, Ratnaparkhi GS. A genetic screen identifies Tor as an interactor of VAPB in a Drosophila m...

Neurodegenerative & neuromuscular disease-related studies--recent reports

Luan Z, Reddig K, Li HS. Loss of Na(+)/K(+)-ATPase in Drosophila photoreceptors leads to blindness and age-dependent neurodegeneration. Exp Neurol. 2014 Nov;261:791-801. doi: 10.1016/j.expneurol.2014.08.025. Epub 2014 PMID: 25205229; PMCID: PMC4194232.

Rosenbaum EE, Vasiljevic E, Cleland SC, Flores C, Colley NJ. The Gos28 SNARE Mediates Intra-Golgi Transport of Rhodopsin and is Required for Photoreceptor Survival. J Biol Chem. 2014 Sep 26. PMID: 25261468.

Barclay SS, Tamura T, Ito H, Fujita K, Tagawa K, Shimamura T, Katsuta A, Shiwaku H, Sone M, Imoto S, Miyano S, Okazawa H. Systems biology analysis of Drosophila in vivo screen data elucidates core networks for DNA damage repair in SCA1. Hum Mol Genet. 2014 Mar 1;23(5):1345-64. doi: 10.1093/hmg/ddt524. PMID: 24179173.  From the abstract: "In this study, we performed a systematic in vivo screen of all available Drosophila melanogaster homolog DNA repair genes, and we tested the effect of their overexpression on lifespan and developmental viability in Spinocerebellar Ataxia Type 1 (SCA1) Drosophila models expressing human mutant Ataxin-1 (Atxn1)."

Xu S, Wilf R, Menon T, Panikker P, Sarthi J, Elefant F. Epigenetic Control of Learning and Memory in Drosophila by Tip60 HAT Action. Genetics. 2014 Oct 17. PMID: 25326235. From the abstract: "Disruption of epigenetic gene control mechanisms in the brain causes significant cognitive impairment that is a debilitating hallmark of most neurodegenerative disorders including Alzheimer's disease (AD). ... Here, we investigate an epigenetic role for the HAT Tip60 in learning and memory formation using the Drosophila CNS mushroom body (MB) as a well-characterized cognition model. ... we find that both learning and immediate recall memory deficits that occur under AD associated amyloid precursor protein (APP) induced neurodegenerative conditions can be effectively rescued by increasing Tip60 HAT levels specifically in the MB. ..."

Stepto A, Gallo JM, Shaw CE, Hirth F. Modelling C9ORF72 hexanucleotide repeat expansion in amyotrophic lateral sclerosis and frontotemporal dementia. Acta Neuropathol. 2014 Mar;127(3):377-89. PMID: 24366528. From the abstract of this review: "... studies using patient-derived cells, as well as Drosophila and zebrafish models overexpressing disease-related hexanucleotide expansions, can cause repeat length-dependent formation of RNA foci, which directly and progressively correlate with cellular toxicity. ..."

Zwarts L, Van Eijs F, Callaerts P. Glia in Drosophila behavior. J Comp Physiol A Neuroethol Sens Neural Behav Physiol. 2014 Oct 22. PMID: 25336160. From the abstract: "... We here summarize recent work describing the role of glia in normal behavior and in Drosophila models for neurological and behavioral disorders."

Fly study relevant to Menkes and Wilson diseases

Hwang JE, de Bruyne M, Warr CG, Burke R. Copper overload and deficiency both adversely affect the central nervous system of Drosophila. Metallomics. 2014 Oct 17. PMID: 25322772.

From the abstract: "The human copper homeostasis disorders Menkes and Wilson disease both have severe neurological symptoms. Menkes is a copper deficiency disorder whereas Wilson disease patients suffer from copper toxicity, indicating that tight control of neuronal copper levels is essential for proper nervous system development and function. Here we examine the consequences of neuronal copper deficiency and excess in the Drosophila melanogaster nervous system, using targeted manipulation of the copper uptake genes Ctr1A and Ctr1B and efflux gene ATP7 in combination with altered dietary copper levels. ... We conclude that both copper overload and excess have detrimental effects on Drosophila neuronal function, reducing overall fly viability as well as impacting on a specific neuropeptide pathway."

Review relevant to Dscam proteins and Down's syndrome

Montesinos ML. Roles for DSCAM and DSCAML1 in central nervous system development and disease. Adv Neurobiol. 2014;8:249-70. PMID: 25300140.

From the abstract: "... In Drosophila, Dscam proteins are involved in neuronal wiring, while in vertebrates, the role of these cell adhesion molecules in neurogenesis, dendritogenesis, axonal outgrowth, synaptogenesis, and synaptic plasticity is only just beginning to be understood. In this chapter, we will review the functions ascribed to the two paralogous proteins found in humans, DSCAM and DSCAML1 (DSCAM-like 1), based on findings in knockout mice. The signaling pathways downstream of DSCAM activation and the role of DSCAM miss-expression in disease will be also discussed, particularly with regard to the intellectual disability in Down's syndrome."

FlyRNAi: Genome-wide RNAi screen related to Parkinson's dis...

FlyRNAi: Genome-wide RNAi screen related to Parkinson's dis...: Ivatt RM, Sanchez-Martinez A, Godena VK, Brown S, Ziviani E, Whitworth AJ. Genome-wide RNAi screen identifies the Parkinson disease GWAS ris...

Review -- fly models of ALS

Casci I, Pandey UB. A fruitful endeavor: Modeling ALS in the fruit fly. Brain Res. 2014 Oct 4. pii: S0006-8993(14)01337-7. PMID: 25289585.

From the abstract: "... Several Drosophila models have now been developed for studying the roles of ALS-associated genes in disease pathogenesis that allowed us to understand the molecular pathways that lead to motor neuron degeneration in ALS patients. Our primary goal in this review is to highlight the lessons we have learned using Drosophila models pertaining to ALS research."

Specific mutations in VPS35 associated with Parkinson's disease tested in flies

Wang HS, Toh J, Ho P, Tio M, Zhao Y, Tan EK. In vivo evidence of pathogenicity of VPS35 mutations in the Drosophila. Mol Brain. 2014 Oct 8;7(1):73. PMID: 25288323.

miRNA study using fly model of Alzheimer's diesase

Kong Y, Wu J, Yuan L. MicroRNA Expression Analysis of Adult-onset Drosophila Alzheimer's Disease Model. Curr Alzheimer Res. 2014 Oct 1. PMID: 25274109.

FlyRNAi: Drosophila cell-based genome-wide screen related t...

FlyRNAi: Drosophila cell-based genome-wide screen related t...: Ivatt RM, Sanchez-Martinez A, Godena VK, Brown S, Ziviani E, Whitworth AJ. Genome-wide RNAi screen identifies the Parkinson disease GWAS ri...

Large-scale study of genes on the fly X-chromosome and of rare variants associated with unsolved diseases

Yamamoto S, Jaiswal M, Charng WL, Gambin T, Karaca E, Mirzaa G, Wiszniewski W, Sandoval H, Haelterman NA, Xiong B, Zhang K, Bayat V, David G, Li T, Chen K, Gala U, Harel T, Pehlivan D, Penney S, Vissers LE, de Ligt J, Jhangiani SN, Xie Y, Tsang SH, Parman Y, Sivaci M, Battaloglu E, Muzny D, Wan YW, Liu Z, Lin-Moore AT, Clark RD, Curry CJ, Link N, Schulze KL, Boerwinkle E, Dobyns WB, Allikmets R, Gibbs RA, Chen R, Lupski JR, Wangler MF, Bellen HJ. A Drosophila Genetic Resource of Mutants to Study Mechanisms Underlying Human Genetic Diseases. Cell. 2014 Sep 25;159(1):200-214. PMID: 25259927.

From the abstract: "... We conducted a mosaic genetic screen of lethal mutations on the Drosophila X chromosome to identify genes required for the development, function, and maintenance of the nervous system. We identified 165 genes, most of whose function has not been studied in vivo. In parallel, we investigated rare variant alleles in 1,929 human exomes from families with unsolved Mendelian disease. Genes that are essential in flies and have multiple human homologs were found to be likely to be associated with human diseases. Merging the human data sets with the fly genes allowed us to identify disease-associated mutations in six families and to provide insights into microcephaly associated with brain dysgenesis. This bidirectional synergism between fly genetics and human genomics facilitates the functional annotation of evolutionarily conserved genes involved in human health."

Anlaysis of a fly Alzheimer's disease model suggests it's not what it might seem

Allan K, Perez KA, Barnham KJ, Camakaris J, Burke R. A commonly used Drosophila model of Alzheimer's disease generates an aberrant species of amyloid-β with an additional N-terminal glutamine residue. FEBS Lett. 2014 Oct 16;588(20):3739-43. PMID: 25171862.

Abstract: "Expression of human amyloid-β (Aβ) in Drosophila is frequently used to investigate its toxicity in vivo. We expressed Aβ1-42 in the fly using a secretion signal derived from the Drosophila necrotic gene, as described in several previous publications. Surface-enhanced laser desorption/ionization TOF MS analysis revealed that the Aβ produced contained an additional glutamine residue at the N-terminus. AβQ+1-42 was found to have increased protein abundance and to cause more severe neurodegenerative effects than wild type Aβ1-42 as assessed by locomotor activity and lifespan assays. These data reveal that a commonly used model of Alzheimer's disease generates incorrect Aβ peptide."

Bromine: You've got to have it

McCall AS, Cummings CF, Bhave G, Vanacore R, Page-McCaw A, Hudson BG. Bromine is an essential trace element for assembly of collagen IV scaffolds in tissue development and architecture. Cell. 2014 Jun 5;157(6):1380-92. PMID: 24906154; PMCID: PMC4144415.

From the abstract: "... Dietary Br deficiency is lethal in Drosophila, whereas Br replenishment restores viability ... Importantly, Br-deficient flies phenocopy the developmental and BM [basement membrane] defects observed in peroxidasin mutants and indicate a functional connection between Br(-), collagen IV, and peroxidasin. We establish that Br(-) is required for sulfilimine formation within collagen IV, an event critical for BM assembly and tissue development. Thus, bromine is an essential trace element for all animals, and its deficiency may be relevant to BM alterations observed in nutritional and smoking-related disease."

Fly study related to pesticide-induced neurotoxicity--links to Parkinson's disease

Cassar M, Issa AR, Riemensperger T, Petitgas C, Rival T, Coulom H, Iché-Torres M, Han KA, Birman S. A dopamine receptor contributes to paraquat-induced neurotoxicity in Drosophila. Hum Mol Genet. 2014 Aug 25. pii: ddu430. PMID: 25158689.

From the abstract: "Long-term exposure to environmental oxidative stressors, like the herbicide paraquat (PQ), has been linked to the development of Parkinson's disease (PD), the most frequent neurodegenerative movement disorder. Paraquat is thus frequently used in the fruit fly Drosophila melanogaster and other animal models to study PD and the degeneration of dopaminergic neurons (DNs) that characterizes this disease. Here, we show that a D1-like dopamine (DA) receptor, DAMB, actively contributes to the fast central nervous system (CNS) failure induced by PQ in the fly. ... Further studies of DAMB signaling in Drosophila could have implications for better understanding DA-related neurodegenerative disorders in humans."

Catching up--papers related to flies and neurodegnerative diseases

Wu K, Liu J, Zhuang N, Wang T. UCP4A protects against mitochondrial dysfunction and degeneration in pink1/parkin models of Parkinson's disease. FASEB J. 2014 Aug 21. pii: fj.14-255802. PMID: 25145627.

Long DM, Blake MR, Dutta S, Holbrook SD, Kotwica-Rolinska J, Kretzschmar D, Giebultowicz JM. Relationships between the Circadian System and Alzheimer's Disease-Like Symptoms in Drosophila. PLoS One. 2014 Aug 29;9(8):e106068. PMID: 25171136; PMCID: PMC4149435.

Dietz KN, Di Stefano L, Maher RC, Zhu H, Macdonald ME, Gusella JF, Walker JA. The Drosophila Huntington's disease gene ortholog dhtt influences chromatin regulation during development. Hum Mol Genet. 2014 Aug 28. pii: ddu446. PMID: 25168387.

New fly Alzheimer's disease model

Mhatre SD, Michelson SJ, Gomes J, Tabb LP, Saunders AJ, Marenda DR. Development and characterization of an aged onset model of Alzheimer's disease in Drosophila melanogaster. Exp Neurol. 2014 Aug 27;261C:772-781. PMID: 25173219.

Review--models of Fragile X-associated primary ovarian insufficiency

Sherman SL, Curnow EC, Easley CA, Jin P, Hukema RK, Tejada MI, Willemsen R, Usdin K. Use of model systems to understand the etiology of fragile X-associated primary ovarian insufficiency (FXPOI). J Neurodev Disord. 2014;6(1):26. PMID: 25147583; PMCID: PMC4139715.

From the abstract: "... Vertebrate (mouse and rat) and invertebrate (Drosophila melanogaster) animal studies for the FMR1 premutation and ovarian function exist and have been instrumental in advancing our understanding of the disease phenotype. ... Here, we review the characterization of the current models and describe the development and potential of the new models. Finally, we will discuss some of the molecular mechanisms that might be responsible for FXPOI."

Flies & SMA

Praveen K, Wen Y, Gray KM, Noto JJ, Patlolla AR, Van Duyne GD, Matera AG. SMA-causing missense mutations in survival motor neuron (Smn) display a wide range of phenotypes when modeled in Drosophila. PLoS Genet. 2014 Aug 21;10(8):e1004489. PMID: 25144193; PMCID: PMC4140637.

Huntington's and the heart

Melkani GC, Trujillo AS, Ramos R, Bodmer R, Bernstein SI, Ocorr K. Huntington's disease induced cardiac amyloidosis is reversed by modulating protein folding and oxidative stress pathways in the Drosophila heart. PLoS Genet. 2013;9(12):e1004024. PMID: 24367279; PMCID: PMC3868535.

From the abstract: "... We conclude that modulation of both protein unfolding and oxidative stress pathways in the Drosophila heart model can ameliorate the detrimental PolyQ effects, thus providing unique insights into the genetic mechanisms underlying amyloid-induced cardiac failure in HD patients."

Review--Drosophila as a model for inflammation, innate immunity and cancer

Wang L, Kounatidis I, Ligoxygakis P. Drosophila as a model to study the role of blood cells in inflammation, innate immunity and cancer. Front Cell Infect Microbiol. 2014 Jan 9;3:113. PMID: 24409421; PMCID: PMC3885817.

Fly study related to spincerebellar ataxia

Liman J, Deeg S, Voigt A, Voßfeldt H, Dohm CP, Karch A, Weishaupt J, Schulz JB, Bähr M, Kermer P. CDK5 protects from caspase-induced Ataxin-3 cleavage and neurodegeneration. J Neurochem. 2014 Jun;129(6):1013-23. PMID: 24548080.

Peripheral motor neuron syndrome study--patient mutations explored using Drosophila

Herrmann DN, Horvath R, Sowden JE, Gonzales M, Sanchez-Mejias A, Guan Z, Whittaker RG, Almodovar JL, Lane M, Bansagi B, Pyle A, Boczonadi V, Lochmüller H, Griffin H, Chinnery PF, Lloyd TE, Littleton JT, Zuchner S. Synaptotagmin 2 mutations cause an autosomal-dominant form of lambert-eaton myasthenic syndrome and nonprogressive motor neuropathy. Am J Hum Genet. 2014 Sep 4;95(3):332-9. PMID: 25192047.

From the abstract: "Synaptotagmin 2 is a synaptic vesicle protein that functions as a calcium sensor for neurotransmission ... Via whole-exome sequencing, we identified heterozygous missense mutations in the C2B calcium-binding domain of the gene encoding Synaptotagmin 2 in two multigenerational families presenting with peripheral motor neuron syndromes. ... Characterization of the mutation homologous to the human c.920A>C variant in Drosophila Synaptotagmin revealed a dominant disruption of synaptic vesicle exocytosis ..."

Review--invertebrate models of coenzyme Q disease

Fernández-Ayala DJ, Jiménez-Gancedo S, Guerra I, Navas P. Invertebrate models for coenzyme q10 deficiency. Mol Syndromol. 2014 Jul;5(3-4):170-9. PMID: 25126050; PMCID: PMC4112529.

New reports--fly models of neurodegenerative diseases

Catching up on neurodegenerative disease-related reports

Fly study related to ALS

Romano G, Klima R, Buratti E, Verstreken P, Baralle FE, Feiguin F. Chronological requirements of TDP-43 function in synaptic organization and locomotive control. Neurobiol Dis. 2014 Aug 1. pii: S0969-9961(14)00201-0. PMID: 25088713.

Mouse study follows up on potential therapeutic approach to HD identified in Drosophila

Arribat Y, Talmat-Amar Y, Paucard A, Lesport P, Bonneaud N, Bauer C, Bec N, Parmentier ML, Benigno L, Larroque C, Maurel P, Maschat F. Systemic delivery of P42 peptide: a new weapon to fight Huntington's disease. Acta Neuropathol Commun. 2014 Aug 5;2(1):86. PMID: 25091984.

Fly study related to frontotemporal dementia and ALS

Mizielinska S, Grönke S, Niccoli T, Ridler CE, Clayton EL, Devoy A, Moens T, Norona FE, Woollacott IO, Pietrzyk J, Cleverley K, Nicoll AJ, Pickering-Brown S, Dols J, Cabecinha M, Hendrich O, Fratta P, Fisher EM, Partridge L, Isaacs AM. C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins. Science. 2014 Aug 7. pii: 1256800. PMID: 25103406.

BMP signaling & neurodegenerative diseases

Kang MJ, Hansen TJ, Mickiewicz M, Kaczynski TJ, Fye S, Gunawardena S. Disruption of Axonal Transport Perturbs Bone Morphogenetic Protein (BMP) - Signaling and Contributes to Synaptic Abnormalities in Two Neurodegenerative Diseases. PLoS One. 2014 Aug 15;9(8):e104617. PMID: 25127478; PMCID: PMC4134223.

Primary fly larval neuron culture system for study of Alzheimer's disease

Saad Y, Segal D, Ayali A. Enhanced Neurite Outgrowth and Branching Precede Increased Amyloid-β-Induced Neuronal Apoptosis in a Novel Alzheimer's Disease Model. J Alzheimers Dis. 2014 Aug 14. PMID:  25125474

Review and reports related to Parkinson's disease

Chen KF, Crowther DC. Insights into amyloid disease from fly models. Essays Biochem. 2014 Aug 18;56(1):69-83. PMID: 25131587.

Varga SJ, Qi C, Podolsky E, Lee D. A new Drosophila model to study the interaction between genetic and environmental factors in Parkinson׳s disease. Brain Res. 2014 Aug 15. pii: S0006-8993(14)01085-3. PMID: 25130663.

Kimura Y, Fukushi J, Hori S, Matsuda N, Okatsu K, Kakiyama Y, Kawawaki J, Kakizuka A, Tanaka K. Different dynamic movements of wild-type and pathogenic VCPs and their cofactors to damaged mitochondria in a Parkin-mediated mitochondrial quality control system. Genes Cells. 2013 Dec;18(12):1131-43. PMID: 24215292.

New fly model of MEGF-associated congenital muscle disease

Draper I, Mahoney LJ, Mitsuhashi S, Pacak CA, Salomon RN, Kang PB. Silencing of Drpr Leads to Muscle and Brain Degeneration in Adult Drosophila. Am J Pathol. 2014 Aug 8. pii: S0002-9440(14)00374-5. PMID: 25111228.

From the abstract: "Mutations in the gene encoding the single transmembrane receptor multiple epidermal growth factor-like domain (MEGF) 10 cause an autosomal recessive congenital muscle disease in humans. ... Drpr is the sole Drosophila homolog of the human genes MEGF10, MEGF11, and MEGF12 (JEDI, PEAR). ... Our analysis of drpr mutant flies revealed muscle degeneration with fiber size variability and vacuolization, as well as reduced motor performance, features that have been observed in human MEGF10 myopathy. ... the absence of functional redundancy for Drpr in Drosophila may help elucidate whether paralogs of MEGF10 in humans (eg, MEGF11) contribute to maintaining wild-type function in the human brain."

Fly model of cardiomyopathy--role for galactokinase

Lee TE, Yu L, Wolf MJ, Rockman HA. Galactokinase Is a Novel Modifier of Calcineurin-Induced Cardiomyopathy in Drosophila. Genetics. 2014 Jul 31. PMID: 25081566.

From the abstract: "Activated/uninhibited calcineurin is both necessary and sufficient to induce cardiac hypertrophy, a condition that often leads to dilated cardiomyopathy, heart failure, and sudden cardiac death. We expressed constitutively active calcineurin in the adult heart of Drosophila melanogaster and identified enlarged cardiac chamber dimensions and reduced cardiac contractility. In addition, expressing constitutively active calcineurin in the fly heart using the Gal4/UAS system induced an increase in heart wall thickness. We performed a targeted genetic screen for modifiers of calcineurin-induced cardiac enlargement ... we generated a model for discovering novel modifiers of calcineurin-induced cardiac enlargement in the fly and identified galactokinase as a previously unknown regulator of calcineurin-induced cardiomyopathy in adult Drosophila."

Review--fly as a model for studying intestinal dysbiosis

Lee KA(1), Lee WJ. Drosophila as a model for intestinal dysbiosis and chronic inflammatory diseases. Dev Comp Immunol. 2014 Jan;42(1):102-10. PubMed ID 23685204

From the abstract: "The association between deregulated intestinal microbial consortia and host diseases has been recognized since the birth of microbiology over a century ago. Intestinal dysbiosis refers to a state where living metazoans harbor harmful intestinal microflora. However, there is still an issue of whether causality arises from the host or the microbe because it is unclear whether deregulation of the gut microbiota community is the consequence or cause of the host disease. Recent studies using Drosophila and its simple microbiota have provided a valuable model system for dissecting the molecular mechanisms of intestinal dysbiosis. In this review, we examine recent exciting observations in Drosophila gut-microbiota interactions ..."

Flies and sea anemones as models for the study of noise-induced hearing loss

Christie KW, Eberl DF. Noise-induced hearing loss: new animal models. Curr Opin Otolaryngol Head Neck Surg. 2014 Aug 8. PMID: 25111054.

From the abstract: "... Work on sea anemone hair bundles, which resemble auditory hair cells, has revealed secretions that exhibit astonishing healing properties ... for damaged hair bundles ... The second model, the Johnston's organ in Drosophila, is also genetically homologous to hair cells and shows noise-induced hearing loss similar to vertebrates. Drosophila offers genetic and molecular insight into noise sensitivity and pathways that can be manipulated to reduce stress and damage from noise. ... Expanding study of these systems may accelerate identification of strategies to reduce or prevent noise damage in the human ear."

Fly models of Parkinson's disease--two new reports

Chen AY, Wilburn P, Hao X, Tully T. Walking Deficits and Centrophobism in an Alpha-Synuclein Fly Model of Parkinson's Disease. Genes Brain Behav. 2014 Aug 12. PMID: 25113870. [NOTE: As of this posting (8/13/14), the PubMed ID brings up an error message.]

Miura E, Hasegawa T, Konno M, Suzuki M, Sugeno N, Fujikake N, Geisler S, Tabuchi M, Oshima R, Kikuchi A, Baba T, Wada K, Nagai Y, Takeda A, Aoki M. VPS35 dysfunction impairs lysosomal degradation of α-synuclein and exacerbates neurotoxicity in a Drosophila model of Parkinson's disease. Neurobiol Dis. 2014 Aug 6. pii: S0969-9961(14)00215-0. PMID: 25107340.

From the abstract: "Mutations in vacuolar protein sorting 35 (VPS35) have been linked to familial Parkinson's disease (PD). ... we found that the knockdown of Drosophila VPS35 not only induced the accumulation of the detergent-insoluble αSYN species in the brain but also exacerbated both locomotor impairments and mild compound eye disorganization and interommatidial bristle loss in flies expressing human αSYN. ..."

Butterflies and disease models? Not quite. Monarch Initiative online resource.

Recently learned about the Monarch Initiative. This site might be of interest to those looking for mouse or other models for the study of disease. 

From their About Monarch page:  "We will provide tools ... to support navigating through multi-scale spatial and temporal phenotypes across in vivo and in vitro model systems in the context of genetic and genomic data. These tools will provide basic and clinical science researchers, informaticists, and medical professionals with an integrated interface and set of discovery tools to reveal the genetic basis of disease, facilitate hypothesis generation, and identify novel candidate drug targets."

Additional of interest: 
The DRSC's DIOPT-DIST disease-gene ortholog search tool
The BDSC's pages on Drosophila models of human diseases

Review--mitochondria and Parkinson's Disease--drawing on results from many species including Drosophila

Haelterman NA, Yoon WH, Sandoval H, Jaiswal M, Shulman JM, Bellen HJ. A mitocentric view of Parkinson's disease. Annu Rev Neurosci. 2014 Jul 8;37:137-59. PMID: 24821430.

From the abstract: "... Here, we attempt to synthesize results from experimental studies in diverse systems to define the precise function of these PD genes, as well as their interplay with other genes that affect mitochondrial function. We propose that subtle mitochondrial defects in combination with other insults trigger the onset and progression of disease, in both familial and idiopathic PD."

Review--Hippo signal transduction pathway in disease

Barron DA, Kagey JD. The role of the Hippo pathway in human disease and tumorigenesis. Clin Transl Med. 2014 Jul 18;3:25. PMID: 25097728.

From the abstract: "The molecular nature of this pathway was first uncovered in Drosophila melanogaster ... The pathway is strongly conserved in humans, rendering Drosophila a suitable and efficient model system to better understand the molecular nature of this pathway. In the present study, we review the current understanding of the molecular mechanism and clinical impact of the Hippo pathway. ... Importantly, deregulated Hippo signaling is frequently observed in human cancers. ..."

Herbal drugs and a Drosophila model of nephrolithiasis (kidney stones)

Wu SY, Shen JL, Man KM, Lee YJ, Chen HY, Chen YH, Tsai KS, Tsai FJ, Lin WY, Chen WC. An emerging translational model to screen potential medicinal plants for nephrolithiasis, an independent risk factor for chronic kidney disease. Evid Based Complement Alternat Med. 2014;2014:972958. PMID: 25097661.

From the abstract: "Pharmacological therapy for urolithiasis using medicinal plants has been increasingly adopted for the prevention of its recurrence. A Drosophila melanogaster model developed for translational research of urolithiasis was applied to evaluate agents with potential antilithic effects and calcium oxalate (CaOx) formation. Potential antilithic herbs were prepared in a mixture of food in a diluted concentration of 5,000 from the original extract with 0.5% ethylene glycol (EG) as the lithogenic agent. ... The crystal formation rate in the EG group was 100.0%. In the study, 16 tested herbal drugs reached the crystal formation rate of 0.0% ... Two herbal drugs ... caused the death of all flies. Our rapid screening methods provided evidence that some medicinal plants have potential antilithic effects. ..."

Review relevant to fly studies of hearing and the development of auditory organs

Prakash Bokolia N, Mishra M. Hearing molecules, mechanism and transportation: Modeled in Drosophila melanogaster. Dev Neurobiol. 2014 Aug 1. PMID: 25081222.

From the abstract: "... The current review describes the similarities and differences between the vertebrate and fly auditory organs at developmental, structural, molecular and transportation levels."

Fly model of calcineurin-induced cardiac hypertrophy uncovers role for galactokinase

Lee TE, Yu L, Wolf MJ, Rockman HA. Galactokinase Is a Novel Modifier of Calcineurin-Induced Cardiomyopathy in Drosophila. Genetics. 2014 Jul 31. PMID: 25081566.

From the abstract: "Activated/uninhibited calcineurin is both necessary and sufficient to induce cardiac hypertrophy, a condition that often leads to dilated cardiomyopathy, heart failure, and sudden cardiac death. ... we generated a model for discovering novel modifiers of calcineurin-induced cardiac enlargement in the fly and identified galactokinase as a previously unknown regulator of calcineurin-induced cardiomyopathy in adult Drosophila."

Drosophila model of complex I dysfunction-type mitochondrial disease

Burman JL, Itsara LS, Kayser EB, Suthammarak W, Wang AM, Kaeberlein M, Sedensky MM, Morgan PG, Pallanck LJ. A Drosophila model of mitochondrial disease caused by a complex I mutation that uncouples proton pumping from electron transfer. Dis Model Mech. 2014 PMID: 25085991.

From the abstract: "Mutations affecting mitochondrial complex I, a multi-subunit assembly that couples electron transfer to proton pumping, are the most frequent cause of heritable mitochondrial diseases. However, the mechanisms by which complex I dysfunction results in disease remain unclear. Here, we describe a Drosophila model of complex I deficiency caused by a homoplasmic mutation in the mitochondrial-encoded NADH dehydrogenase subunit 2 (ND2) gene. ... our findings support the model that diminished respiratory chain activity, and consequent energy deficiency, are responsible for the pathogenesis of complex I-associated neurodegeneration."

Gal4 lines for larval CNS studies

If you are interested to use the Gal4-UAS system to express genes in the larval central nervous system (CNS) as part of your human disease model or other Drosophila studies, check out this post at FlyRNAi--recent paper describes >6,000 larval CNS Gal4 lines.

Review--flies, chromatin remodeling, and intellectual disability & neural disorders

Taniguchi H, Moore AW. Chromatin regulators in neurodevelopment and disease: Analysis of fly neural circuits provides insights: Networks of chromatin regulators and transcription factors underlie Drosophila neurogenesis and cognitive defects in intellectual disability and neuropsychiatric disorder models. Bioessays. 2014 Jul 28. PMID: 25067789.

At least the following disabilities, disorders or syndromes are mentioned in the review (Blogger does not allow tagging the entry with so many characters):  Intellectual disability, Schizophrenia, Autism, CHARGE syndrome, Coffin-Siris syndrome, Kabuki syndrome, Kleefstra syndrome, Maat-Kievit-Brunner syndrome, Nicolaides-Baraitser syndrome, Rubinstein-Taybi syndrome, Say-Barber-Biesecker-Young-Simpson syndrome, Schinzel-Giedion syndrome, Sotos syndrome, Weaver syndrome, Wiedemann-Steiner syndrome

Research article and dispatch--Cancer-related study in flies

Herranz H, Weng R, Cohen SM. Crosstalk between Epithelial and Mesenchymal Tissues in Tumorigenesis and Imaginal Disc Development. Curr Biol. 2014 Jul 7;24(13):1476-84. PMID: 24980505.
From the abstract: "... Here, we report a Drosophila genetic model of EGFR-driven tumorigenesis in which the neoplastic transformation depends on interaction between epithelial and mesenchymal cells. ... Tumorigenesis in this model co-opts a regulatory mechanism that is normally involved in controlling growth of the imaginal disc during development."

See also a dispatch on the article: Milán M. Tumor Models: Tumor-Stroma Interactions Drive Neoplastic Transformation in Drosophila. Curr Biol. 2014 Jul 21;24(14):R658-R659. PMID: 25050966.

Review--Drosophila as a model to study nanotoxicity

Ong C, Yung LY, Cai Y, Bay BH, Baeg GH. Drosophila melanogaster as a model organism to study nanotoxicity. Nanotoxicology. 2014 Jul 22:1-8. PMID: 25051331.

From the abstract: "... The incorporation of nanomaterials into consumer and biomedical products is a cause for concern as nanomaterials are often associated with toxicity in many in vitro studies. In vivo animal studies of the toxicity of nanomaterials with rodents and other mammals are, however, limited ... Drosophila, a genetically tractable organism with distinct developmental stages and short life cycle, serves as an ideal organism to study nanomaterial-mediated toxicity ...

Fly study on activity and stability of Retinoblastoma protein

Zhang L, Wei Y, Pushel I, Heinze K, Elenbaas J, Henry RW, Arnosti DN. Integrated Stability and Activity Control of the Drosophila Rbf1 Retinoblastoma Protein. J Biol Chem. 2014 Jul 21. pii: jbc.M114.586818. PMID: 25049232.

Drosophila as an in vivo system to study possible anti-cancer effects of a peptide from soy

Jones G, Srivastava A. Understanding Lunasin's biology and potential as a cancer therapeutic by utilizing Drosophila genetics. Exp Biol Med (Maywood). 2014 May;239(5):519-28. Review. PMID: 24625440.

"Soy contains many bioactive molecules known to elicit anticancer effects. One such peptide, Lunasin, has been shown to selectively act on newly transformed cells ... Lunasin's efficacy in an in vivo system is yet to be assessed. ... we discuss the state of knowledge with respect to Lunasin and then review some of the powerful genetic tools available in Drosophila. ..."

Fly study suggests role for cation-chloride cotransporters in glia in seizure disorders

Rusan ZM, Kingsford OA, Tanouye MA. Modeling Glial Contributions to Seizures and Epileptogenesis: Cation-Chloride Cotransporters in Drosophila melanogaster. PLoS One. 2014 Jun 27;9(6):e101117. PMID: 24971529; PMCID: PMC4074161.

From the abstract: "Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. ... Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi) of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. ... The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed."

Study of FDA-approved drugs in flies points to possible combined therapies for cancer treatment

Markstein M, Dettorre S, Cho J, Neumüller RA, Craig-Müller S, Perrimon N. Systematic screen of chemotherapeutics in Drosophila stem cell tumors. Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4530-5. PMID: 24616500; PMCID: PMC3970492.

From the abstract: "Here we report the development of an in vivo system to study the interaction of stem cells with drugs using a tumor model in the adult Drosophila intestine. ... These results reveal an unanticipated side effect on stem cells that may contribute to tumor recurrence. ... An immediate implication of our findings is that supplementing traditional chemotherapeutics with anti-inflammatories may reduce tumor recurrence."

Succinate Dehydrogenase-related neurodegeneration and cancers--study in yeast, flies and mammalian cells

Van Vranken JG, Bricker DK, Dephoure N, Gygi SP, Cox JE, Thummel CS, Rutter J. SDHAF4 Promotes Mitochondrial Succinate Dehydrogenase Activity and Prevents Neurodegeneration. Cell Metab. 2014 Jun 18. pii: S1550-4131(14)00220-4. PMID: 24954416.

From the abstract: "Succinate dehydrogenase (SDH) occupies a central place in cellular energy production, linking the tricarboxylic cycle with the electron transport chain. As a result, a subset of cancers and neuromuscular disorders result from mutations affecting any of the four SDH structural subunits or either of two known SDH assembly factors. Herein we characterize an evolutionarily conserved SDH assembly factor designated Sdh8/SDHAF4, using yeast, Drosophila, and mammalian cells. ... These studies provide insights into the mechanisms by which SDH is assembled and raise the possibility that some forms of neuromuscular disease may be associated with mutations that affect this SDH assembly factor."

Catching up on neurodegenerative disease-related reports--Parkinson's disease, Fragile X syndrome, ALS

Parkinson's disease

Chuang CL, Lu YN, Wang HC, Chang HY. Genetic dissection reveals that Akt is the critical kinase downstream of LRRK2 to phosphorylate and inhibit FOXO1, and promotes neuron survival. Hum Mol Genet. 2014 Jun 10. PMID: 24916379. [fly and rat studies]

Hwang RD, Wiemerslage L, LaBreck CJ, Khan M, Kannan K, Wang X, Zhu X, Lee D, Fridell YW. The neuroprotective effect of human uncoupling protein 2 (hUCP2) requires cAMP-dependent protein kinase in a toxin model of Parkinson's disease. Neurobiol Dis. 2014 Sep;69:180-91. PMID: 24965893.

Ivatt RM, Whitworth AJ. SREBF1 links lipogenesis to mitophagy and sporadic Parkinson disease. Autophagy. 2014 Jun 27;10(8). Review. PMID: 24991824.

Bingol B, Tea JS, Phu L, Reichelt M, Bakalarski CE, Song Q, Foreman O, Kirkpatrick DS, Sheng M. The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy. Nature. 2014 Jun 19;510(7505):370-5. PMID: 24896179.

Fragile X syndrome

He F, Krans A, Freibaum BD, Taylor JP, Todd PK. TDP-43 suppresses CGG repeat-induced neurotoxicity through interactions with HnRNP A2/B1. Hum Mol Genet. 2014 May 8. PMID: 24920338. [From the abstract: "... suggest a convergence of pathogenic cascades between repeat expansion disorders and RNA-binding proteins implicated in neurodegenerative disease."]

Friedman SH, Dani N, Rushton E, Broadie K. Fragile X mental retardation protein regulates trans-synaptic signaling in Drosophila. Dis Model Mech. 2013 Nov;6(6):1400-13. PMID: 24046358; PMCID: PMC3820263.

ALS

Miskiewicz K, Jose LE, Yeshaw WM, Valadas JS, Swerts J, Munck S, Feiguin F, Dermaut B, Verstreken P. HDAC6 Is a Bruchpilot Deacetylase that Facilitates Neurotransmitter Release. Cell Rep. 2014 Jul 10;8(1):94-102. PMID: 24981865.

Study explores Nedd4 role in fly and rat models of Parkinson's disease

Davies SE, Hallett PJ, Moens T, Smith G, Mangano E, Kim HT, Goldberg AL, Liu JL, Isacson O, Tofaris GK. Enhanced ubiquitin-dependent degradation by Nedd4 protects against α-synuclein accumulation and toxicity in animal models of Parkinson's disease. Neurobiol Dis. 2014 Apr;64:79-87. PMID: 24388974; PMCID: PMC3988924.

Effects of gene knockdown and polyphenol gallic acid in a fly model of Parkinson's disease

Ortega-Arellano HF, Jimenez-Del-Rio M, Velez-Pardo C. Dmp53, basket and drICE gene knockdown and polyphenol gallic acid increase life span and locomotor activity in a Drosophila Parkinson's disease model. Genet Mol Biol. 2013 Dec;36(4):608-15. PMID: 24385865; PMCID: PMC3873193.

Diabetes-related fly study: from human GWAS data to fly disease model

He BZ, Ludwig MZ, Dickerson DA, Barse L, Arun B, Vilhjálmsson BJ, Jiang P, Park SY, Tamarina NA, Selleck SB, Wittkopp PJ, Bell GI, Kreitman M. Effect of genetic variation in a Drosophila model of diabetes-associated misfolded human proinsulin. Genetics. 2014 Feb;196(2):557-67. PMID: 24281155; PMCID: PMC3914626.

From the abstract: "The identification and validation of gene-gene interactions is a major challenge in human studies. Here, we explore an approach for studying epistasis in humans using a Drosophila melanogaster model of neonatal diabetes mellitus. ... In conclusion, the ability to create a model of human genetic disease, map a QTL by GWAS to a specific gene, and validate its contribution to disease with available genetic resources and the potential to experimentally link the variant to a molecular mechanism demonstrate the many advantages Drosophila holds in determining the genetic underpinnings of human disease."

Fly study points to mechanisms for the Netrin and Deleted in Colorectal Carcinoma (DCC) proteins

Manhire-Heath R, Golenkina S, Saint R, Murray MJ. Netrin-dependent downregulation of Frazzled/DCC is required for the dissociation of the peripodial epithelium in Drosophila. Nat Commun. 2013;4:2790. PMID: 24225841.

From the abstract: "Netrins are secreted chemoattractants with roles in axon guidance, cell migration and epithelial plasticity. Netrin-1 also promotes the survival of metastasized cells by inhibiting the pro-apoptotic effects of its receptor Deleted in Colorectal Carcinoma (DCC). Here we report that Netrins can also regulate epithelial dissociation during Drosophila wing eversion. ... we provide evidence that Frazzled acts through the ERM-family protein Moesin to inhibit eversion. This mechanism may also help explain the role of Netrin and DCC in cancer metastasis."

Fly studies help define conserved gene networks related to intellectual disability

Now free in PubMed Central:

Oortveld MA, Keerthikumar S, Oti M, Nijhof B, Fernandes AC, Kochinke K, Castells-Nobau A, van Engelen E, Ellenkamp T, Eshuis L, Galy A, van Bokhoven H, Habermann B, Brunner HG, Zweier C, Verstreken P, Huynen MA, Schenck A. Human intellectual disability genes form conserved functional modules in Drosophila. PLoS Genet. 2013 Oct;9(10):e1003911. PMID: 24204314; PMCID: PMC3814316.

From the abstract: “Intellectual Disability (ID) disorders, defined by an IQ below 70, are genetically and phenotypically highly heterogeneous. Identification of common molecular pathways underlying these disorders is crucial for understanding the molecular basis of cognition and for the development of therapeutic intervention strategies. To systematically establish their functional connectivity, we used transgenic RNAi to target 270 ID gene orthologs in the Drosophila eye. Assessment of neuronal function in behavioral and electrophysiological assays and multiparametric morphological analysis identified phenotypes associated with knockdown of 180 ID gene orthologs. Most of these genotype-phenotype associations were novel. ... Drosophila phenotype groups show, in addition to ID, significant phenotypic similarity also in humans, indicating that functional modules are conserved. The combined data indicate that ID disorders, despite their extreme genetic diversity, are caused by disruption of a limited number of highly connected functional modules.”

Fly as a model for studying wound healing--review article

Muñoz-Soriano V, López-Domenech S, Paricio N. Why mammalian wound healing researchers may wish to turn to Drosophila as a model. Exp Dermatol. 2014 Jun 18. doi: 10.1111/exd.12472. PMID: 24942366.

From the abstract:  "In this paper, we discuss the benefits and limitations of using Drosophila in wound healing research, especially presenting this organism as a promising tool for the identification of new therapeutic targets and drugs in this context."

Prickle modulation of vesicle transport--relevance to seisure disorders

Big thanks to the BDSC for the heads up on this paper related to seizure disorders.

Salleh N. Ehaideb, Atulya Iyengar, Atsushi Ueda, Gary J. Iacobucci, Cathryn Cranston, Alexander G. Bassuk, David Gubb, Jeffrey D. Axelrod, Shermali Gunawardena, Chun-Fang Wua, and J. Robert Manaka (2014) prickle modulates microtubule polarity and axonal transport to ameliorate seizures in flies. PNAS.

From the abstract: "Recent analyses in flies, mice, zebrafish, and humans showed that mutations in prickle orthologs result in epileptic phenotypes, although the mechanism responsible for generating the seizures was unknown. Here, we show that Prickle organizes microtubule polarity and affects their growth dynamics in axons of Drosophila neurons, which in turn influences both anterograde and retrograde vesicle transport. ... These data reveal a previously unidentified pathway in the pathophysiology of seizure disorders and provide evidence for a more generalized cellular mechanism whereby Prickle mediates polarity by influencing microtubule-mediated transport."

Drosophila cancer-related screen of FDA drugs

Markstein M, Dettorre S, Cho J, Neumüller RA, Craig-Müller S, Perrimon N. Systematic screen of chemotherapeutics in Drosophila stem cell tumors. Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4530-5. doi: 10.1073/pnas.1401160111. PMID: 24616500; PMCID: PMC3970492.

From the abstract:  "Here we report the development of an in vivo system to study the interaction of stem cells with drugs using a tumor model in the adult Drosophila intestine. ... An immediate implication of our findings is that supplementing traditional chemotherapeutics with anti-inflammatories may reduce tumor recurrence."

Fly study relevant to Parkinson's disease links LRRK2 with Akt, FOXO1 and apoptosis

Chuang CL, Lu YN, Wang HC, Chang HY. Genetic dissection reveals that Akt is the critical kinase downstream of LRRK2 to phosphorylate and inhibit FOXO1, and promotes neuron survival. Hum Mol Genet. 2014 Jun 10. PMID: 24916379.

From the abstract: "... Here, we show that LRRK2 protects neurons against apoptosis induced by the Drosophila genes grim, hid and reaper. ... These data establish that LRRK2 can protect neurons from apoptotic insult through a survival pathway in which LRRK2 signals to activate Akt, and then inhibits FOXO1. These results might indicate that a therapeutic pathway to promote neuron survival and to prevent neurodegeneration in Parkinson's disease."

Study of normal function of Tau in flies includes report of partial rescue of Tau mutant with human Tau

Bolkan BJ, Kretzschmar D. Loss of Tau results in defects in photoreceptor development and progressive neuronal degeneration in Drosophila. Dev Neurobiol. 2014 Jun 7. PMID: 24909306.

From the abstract: "... Expression of wild type human Tau partially rescued the neurodegenerative phenotype caused by the loss of endogenous dTau, suggesting that the functions of Tau proteins are functionally conserved from flies to humans."

Cold temperature & fly models of Hereditary Spastic Paraplegia

Baxter SL, Allard DE, Crowl C, Sherwood NT. Cold temperature improves mobility and survival in drosophila models of Autosomal-Dominant Hereditary Spastic Paraplegia (AD-HSP). Dis Model Mech. 2014 Jun 6. pii: dmm.013987. PMID: 24906373.

Two new reports related to Parkinson's disease

Yun J, Puri R, Yang H, Lizzio MA, Wu C, Sheng ZH, Guo M. MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and compensates for loss of PINK1/parkin. Elife. 2014 Jun 4;3:e01958. PMID: 24898855.

From the abstract:  "In this study, we show that MUL1 suppresses PINK1 or parkin mutant phenotypes in Drosophila. ... We further show that removing MUL1 in PINK1 or parkin loss-of-function mutant aggravates phenotypes caused by loss of either gene alone ... Together, these observations show that MUL1 acts in parallel to the PINK1/parkin pathway on a shared target mitofusin to maintain mitochondrial integrity. The MUL1 pathway compensates for loss of PINK1/parkin in both Drosophila and mammals and is a promising therapeutic target for PD."

Shiba-Fukushima K, Inoshita T, Hattori N, Imai Y. PINK1-Mediated Phosphorylation of Parkin Boosts Parkin Activity in Drosophila. PLoS Genet. 2014 Jun 5;10(6):e1004391. PMID: 24901221.

From the abstract:  "Two genes linked to early onset Parkinson's disease, PINK1 and Parkin, encode a protein kinase and a ubiquitin-ligase, respectively. Both enzymes have been suggested to support mitochondrial quality control. ... Our data reveal that Parkin phosphorylation regulates not only mitochondrial function but also the neuronal activity of dopaminergic neurons in vivo, suggesting that the appropriate regulation of Parkin phosphorylation is important for muscular and dopaminergic functions."

Fly model included in new study related to familial encephalopathy with neuroserpin inclusion bodies (FENIB)

Roussel BD, Newton TM, Malzer E, Simecek N, Haq I, Thomas SE, Burr ML, Lehner PJ, Crowther DC, Marciniak SJ, Lomas DA. Sterol metabolism regulates neuroserpin polymer degradation in the absence of the unfolded protein response in the dementia FENIB. Hum Mol Genet. 2013 Nov 15;22(22):4616-26. PMID: 23814041; PMCID: PMC3889810.

Cancer review includes "intriguing new systems using Drosophila and zebrafish"

Kegelman TP, Hu B, Emdad L, Das SK, Sarkar D, Fisher PB. In vivo modeling of malignant glioma: the road to effective therapy. Adv Cancer Res. 2014;121:261-330. PMID: 24889534.

From the abstract: "... This review examines recent developments in the animal modeling of glioma, from more established rat models to intriguing new systems using Drosophila and zebrafish that set the stage for higher throughput studies of potentially useful targets. It also addresses the versatility of mouse modeling ..."

Review--Drosophila as a model for development of novel therapeutics to fight infection

Tzelepis I, Kapsetaki SE, Panayidou S, Apidianakis Y. Drosophila melanogaster: a first step and a stepping-stone to anti-infectives. Curr Opin Pharmacol. 2013 Oct;13(5):763-8. PMID: 23992884.

From the abstract: "Following an expansion in the antibiotic drug discovery in the previous century, we now face a bottleneck in the production of new anti-infective drugs. ... Drug screening in Drosophila offers to fill the gap between in vitro and mammalian model host testing ... alternative screening methods in Drosophila, while low-throughput, may reduce the cost and increase the success rate of preclinical trials."

Review on NPT2b in chronic kidney disease includes discussion of fly studies

Sabbagh Y, Schiavi SC. Role of NPT2b in health and chronic kidney disease. Curr Opin Nephrol Hypertens. 2014 May 20. PMID: 24848935.

Recent fly studies and reviews related to cancer

Sechi S, Colotti G, Belloni G, Mattei V, Frappaolo A, Raffa GD, Fuller MT, Giansanti MG. GOLPH3 Is Essential for Contractile Ring Formation and Rab11 Localization to the Cleavage Site during Cytokinesis in Drosophila melanogaster. PLoS Genet. 2014 May 1;10(5):e1004305. PMID: 24786584; PubMed Central PMCID: PMC4006750.

Huo G, Lu J, Qu Z, Lin Z, Zhang D, Yang Y, Li B. [The applications and advantages of Drosophila melanogaster in cancer research]. Yi Chuan. 2014 Jan;36(1):30-40. Chinese. PubMed PMID: 24846916.

Reddy BA, van der Knaap JA, Bot AG, Mohd-Sarip A, Dekkers DH, Timmermans MA, Martens JW, Demmers JA, Verrijzer CP. Nucleotide biosynthetic enzyme GMP synthase is a TRIM21-controlled relay of p53 stabilization. Mol Cell. 2014 Feb 6;53(3):458-70. PMID: 24462112.  From the abstract: "... Here, we show that guanosine 5'-monophosphate synthase (GMPS) is required for USP7-mediated stabilization of p53. ... Intriguingly, cytoplasmic sequestration of GMPS requires ubiquitylation by TRIM21, a ubiquitin ligase associated with autoimmune disease. These results implicate a classic nucleotide biosynthetic enzyme and a ubiquitin ligase, better known for its role in autoimmune disease, in p53 control."

Markstein M. Modeling colorectal cancer as a 3-dimensional disease in a dish: the case for drug screening using organoids, zebrafish, and fruit flies. Drug Discov Today Technol. 2013 Spring;10(1):e73-81. PMID: 24050233. From the abstract: "This review discusses recent shifts in the understanding of colorectal cancer ... recent advances in the culturing of colorectal stem cells using mammalian organoids, zebrafish, and Drosophila offer promising avenues for anti-CSC drug discovery."

Das TK, Cagan RL. A Drosophila approach to thyroid cancer therapeutics. Drug Discov Today Technol. 2013 Spring;10(1):e65-71. doi: 10.1016/j.ddtec.2012.09.004. PMID: 24050232; PubMed Central PMCID: PMC3779345. From the abstract: "Thyroid neoplasias represent among the fastest growing cancers. ... recent Drosophila models have proven useful both for understanding disease mechanism as well as helping identify new generation therapeutics"

Lourenço FC, Munro J, Brown J, Cordero J, Stefanatos R, Strathdee K, Orange C, Feller SM, Sansom OJ, Vidal M, Murray GI, Olson MF. Reduced LIMK2 expression in colorectal cancer reflects its role in limiting stem cell proliferation. Gut. 2014 Mar;63(3):480-93. PMID: 23585469; PubMed Central PMCID: PMC3932979.

Methods review--use of Drosophila for heart-disease related studies

Ocorr K, Vogler G, Bodmer R. Methods to assess Drosophila heart development, function and aging. Methods. 2014 Apr 12. pii: S1046-2023(14)00133-9. PMID: 24727147.

From the abstract: "In recent years the Drosophila heart has become an established model for many different aspects of human cardiac disease. This model has allowed identification of disease-causing mechanisms underlying congenital heart disease and cardiomyopathies and has permitted the study of underlying genetic, metabolic and age-related contributions to heart function. In this review we discuss methods currently employed in the analysis of the Drosophila heart structure and function ..."

New fly studies and review related to neurodegenerative diseases

Parkinson's-related studies:

Thomas RE, Andrews LA, Burman JL, Lin WY, Pallanck LJ. PINK1-Parkin Pathway Activity Is Regulated by Degradation of PINK1 in the Mitochondrial Matrix. PLoS Genet. 2014 May 29;10(5):e1004279. PMID: 24874806.

Chen AY, Xia S, Wilburn P, Tully T. Olfactory Deficits in an Alpha-Synuclein Fly Model of Parkinson's Disease. PLoS One. 2014 May 30;9(5):e97758. PMID: 24879013.

Martin I, Kim JW, Lee BD, Kang HC, Xu JC, Jia H, Stankowski J, Kim MS, Zhong J, Kumar M, Andrabi SA, Xiong Y, Dickson DW, Wszolek ZK, Pandey A, Dawson TM, Dawson VL. Ribosomal protein s15 phosphorylation mediates LRRK2 neurodegeneration in Parkinson's disease. Cell. 2014 Apr 10;157(2):472-85. PMID: 24725412.

Cornelissen T, Haddad D, Wauters F, Van Humbeeck C, Mandemakers W, Koentjoro B, Sue C, Gevaert K, De Strooper B, Verstreken P, Vandenberghe W. The deubiquitinase USP15 antagonizes Parkin-mediated mitochondrial ubiquitination and mitophagy. Hum Mol Genet. 2014 May 22. PMID: 24852371.

Siddique YH, Naz F, Jyoti S. Effect of curcumin on lifespan, activity pattern, oxidative stress, and apoptosis in the brains of transgenic Drosophila model of Parkinson's disease. Biomed Res Int. 2014;2014:606928. PMID: 24860828; PubMed Central PMCID: PMC4016861.

Shukla AK, Pragya P, Chaouhan HS, Tiwari AK, Patel DK, Abdin MZ, Chowdhuri DK. Heat Shock Protein-70 (Hsp-70) Suppresses Paraquat-Induced Neurodegeneration by Inhibiting JNK and Caspase-3 Activation in Drosophila Model of Parkinson's Disease. PLoS One. 2014 Jun 2;9(6):e98886. PMID: 24887138.

Knight AL, Yan X, Hamamichi S, Ajjuri RR, Mazzulli JR, Zhang MW, Daigle JG, Zhang S, Borom AR, Roberts LR, Lee SK, DeLeon SM, Viollet-Djelassi C, Krainc D, O'Donnell JM, Caldwell KA, Caldwell GA. The Glycolytic Enzyme, GPI, Is a Functionally Conserved Modifier of Dopaminergic Neurodegeneration in Parkinson's Models. Cell Metab. 2014 May 28. PMID: 24882066.

ALS-related studies:

Hans F, Fiesel FC, Strong JC, Jäckel S, Rasse TM, Geisler S, Springer W, Schulz JB, Voigt A, Kahle PJ. UBE2E ubiquitin-conjugating enzymes and ubiquitin isopeptidase Y regulate TDP-43 ubiquitinylation. J Biol Chem. 2014 May 13. PMID: 24825905.

Salado IG, Redondo M, Bello ML, Perez C, Liachko NF, Kraemer BC, Miguel L, Lecourtois M, Gil C, Martinez A, Perez DI. Protein kinase CK-1 inhibitors as new potential drugs for amyotrophic lateral sclerosis. J Med Chem. 2014 Mar 27;57(6):2755-72. PMID: 24592867; PubMed Central PMCID: PMC3969104.

Huntington's-related studies:

O'Rourke JG, Gareau JR, Ochaba J, Song W, Raskó T, Reverter D, Lee J, Monteys AM, Pallos J, Mee L, Vashishtha M, Apostol BL, Nicholson TP, Illes K, Zhu YZ, Dasso M, Bates GP, Difiglia M, Davidson B, Wanker EE, Marsh JL, Lima CD, Steffan JS, Thompson LM. SUMO-2 and PIAS1 modulate insoluble mutant huntingtin protein accumulation. Cell Rep. 2013 Jul 25;4(2):362-75. PMID: 23871671; PubMed Central PMCID: PMC3931302.

SCA-related study:

Jia DD, Zhang L, Chen Z, Wang CR, Huang FZ, Duan RH, Xia K, Tang BS, Jiang H. Lithium chloride alleviates neurodegeneration partly by inhibiting activity of GSK3β in a SCA3 Drosophila model. Cerebellum. 2013 Dec;12(6):892-901. PMID: 23812869.

SMA-related study:

Wishart TM, Mutsaers CA, Riessland M, Reimer MM, Hunter G, Hannam ML, Eaton SL, Fuller HR, Roche SL, Somers E, Morse R, Young PJ, Lamont DJ, Hammerschmidt M, Joshi A, Hohenstein P, Morris GE, Parson SH, Skehel PA, Becker T, Robinson IM, Becker CG, Wirth B, Gillingwater TH. Dysregulation of ubiquitin homeostasis and β-catenin signaling promote spinal muscular atrophy. J Clin Invest. 2014 Apr 1;124(4):1821-34.  PMID: 24590288; PubMed Central PMCID: PMC3973095.

Review:

Lee S, Bang SM, Lee JW, Cho KS. Evaluation of Traditional Medicines for Neurodegenerative Diseases Using Drosophila Models. Evid Based Complement Alternat Med. 2014;2014:967462. Review. PubMed PMID: 24790636; PubMed Central PMCID: PMC3984789.

Fly study reports uncovering a nuclear role for FMRP.

Zhang W, Cheng Y, Li Y, Chen Z, Jin P, Chen D. A feed-forward mechanism involving Drosophila fragile X mental retardation protein triggers a replication stress-induced DNA damage response. Hum Mol Genet. 2014 May 15. pii: ddu241. PMID: 24833720.

From the abstract: "Fragile X syndrome, a common form of inherited mental retardation, is caused by loss of the fragile X mental retardation protein (FMRP). ... Here we show that Drosophila dFMR1 in nucleus is required for replication stress-induced H2Av phosphorylation in the DNA damage response (DDR). ..."

Addressing metabolic issues in a fly model of Adenine Nuclear Translocase (ANT) insufficiency

Vartiainen S, Chen S, George J, Tuomela T, Luoto KR, O'Dell KM, Jacobs HT. Phenotypic rescue of a Drosophila model of mitochondrial ANT1 disease. Dis Model Mech. 2014 May 8. PMID: 24812436.

From the abstract: "... Our findings illustrate the potential of different therapeutic strategies for ANT-linked diseases, based on increasing mitochondrial bioenergy production, or on alleviating metabolic stress."

Two papers--flies and neurodegenerative disease--including a fluorescent protein-based fly eye assay

There are more papers to catch up on but in the meantime, these caught my eye today:

Rumpf S, Bagley JA, Thompson-Peer KL, Zhu S, Gorczyca D, Beckstead RB, Jan LY, Jan YN. Drosophila Valosin-Containing Protein is required for dendrite pruning through a regulatory role in mRNA metabolism. Proc Natl Acad Sci U S A. 2014 May 5. PMID: 24799714.

Burr AA, Tsou WL, Ristic G, Todi SV. Using membrane-targeted green fluorescent protein to monitor neurotoxic protein-dependent degeneration of Drosophila Eyes. J Neurosci Res. 2014 May 2. PMID: 24798551. From the abstract: "Here, we describe a sensitive fluorescence-based method to observe, monitor, and quantify mild Drosophila eye degeneration caused by various proteins, including the polyglutamine disease proteins ataxin-3 (spinocerebellar ataxia type 3) and huntingtin (Huntington's disease), mutant α-synuclein (Parkinson's disease), and Aβ42 (Alzheimer's disease). We show that membrane-targeted green fluorescent protein reports degeneration robustly and quantitatively. This simple yet powerful technique, which is amenable to large-scale screens, can help accelerate studies to understand age-related degeneration and to find factors that suppress it for therapeutic purposes."

Drosophila and the heart--SERCA study

Abraham DM, Wolf MJ. Disruption of sarcoendoplasmic reticulum calcium ATPase function in Drosophila leads to cardiac dysfunction. PLoS One. 2013 Oct 3;8(10):e77785. PMID: 24098595; PMCID: PMC3789689.

From the abstract: "... we show that disruption of CaP60A in a cardiac specific manner results in cardiac dilation and dysfunction ... In addition, the co-expression of a calcium release channel mutation with CaP60A (kum170) is sufficient to rescue the cardiac phenotype but not paralysis. Finally, we show that CaP60A overexpression is able to rescue cardiac function in a model of Drosophila cardiac dysfunction similar to what is observed in mammals ..."

Review of enhancers and "enhanceropathies" includes discussion of several fly studies

Smith E, Shilatifard A. Enhancer biology and enhanceropathies. Nat Struct Mol Biol. 2014 Mar;21(3):210-9. PMID: 24599251.

Parkinson's-related PINK1 study includes mouse and fly assays

Morais VA, Haddad D, Craessaerts K, De Bock PJ, Swerts J, Vilain S, Aerts L, Overbergh L, Grünewald A, Seibler P, Klein C, Gevaert K, Verstreken P, De Strooper B. PINK1 loss-of-function mutations affect mitochondrial complex I activity via NdufA10 ubiquinone uncoupling. Science. 2014 Apr 11;344(6180):203-7. PMID: 24652937.

Editorial suggests use of Drosophila in studies related to nanotoxicology and nanomedicine

Vecchio G. A fruit fly in the nanoworld: once again Drosophila contributes to environment and human health. Nanotoxicology. 2014 Apr 28. PMID: 24766263.

From the abstract: "... The aim of this editorial is to encourage the use of Drosophila by the different research groups working in the fields of nanotoxicology and nanomedicine, in order to define the effects induced by nanomaterials at molecular level for their subsequent exploitation in the field of nanomedicine."

Review--fly neurobiology and cancer

Jiang Y, Reichert H. Drosophila neural stem cells in brain development and tumor formation. J Neurogenet. 2014 Apr 28. PMID: 24766377.

From the abstract: "Here, we review the molecular genetics of Drosophila neuroblasts and discuss some recent advances in stem cell and cancer biology using this model system."

Hedgehog signaling and cilia--fly study related to a variety of human diseases

Kuzhandaivel A, Schultz SW, Alkhori L, Alenius M. Cilia-Mediated Hedgehog Signaling in Drosophila. Cell Rep. 2014 Apr 23. pii: S2211-1247(14)00249-6. PMID: 24768000.

From the abstract: "Cilia mediate Hedgehog (Hh) signaling in vertebrates and Hh deregulation results in several clinical manifestations, such as obesity, cognitive disabilities, developmental malformations, and various cancers. ... We demonstrate that several fundamental key aspects of the vertebrate cilia pathway ... are present in Drosophila. ... our data demonstrate that Hh signaling in Drosophila can be mediated by two pathways and that the ciliary Hh pathway is conserved from Drosophila to vertebrates."

Review looks at Drososophila models of metabolism-related diseases including diabetes

Padmanabha D, Baker KD. Drosophila gains traction as a repurposed tool to investigate metabolism. Trends Endocrinol Metab. 2014 Apr 22. pii: S1043-2760(14)00058-7. PMID: 24768030.

From the abstract: "... the Drosophila system is being used to identify human disease genes and has the potential to model successfully human disorders that center on excessive caloric intake and metabolic dysfunction, including diet-induced lipotoxicity and type 2 diabetes. ..."

Review asks if Drosophila can be used as a model for study of Williams syndrome

Nikitina EA, Medvedeva AV, Zakharov GA, Savvateeva-Popova EV. Williams syndrome as a model for elucidation of the pathway genes - the brain - cognitive functions: genetics and epigenetics. Acta Naturae. 2014 Jan;6(1):9-22. PubMed PMID: 24772323.

From the abstract: "This review tackles the following problems: is it possible to develop relatively simple model systems to analyze the contribution of both a single gene and the consequences of its epigenetic regulation in the formation of the Williams syndrome's cognitive phenotype? Is it possible to use Drosophila as a simple model system?"

New review--Drosophila studies and neurodegenerative diseases

Charng WL, Yamamoto S, Bellen HJ. Shared mechanisms between Drosophila peripheral nervous system development and human neurodegenerative diseases. Curr Opin Neurobiol. 2014 Apr 21;27C:158-164. PMID: 24762652.

Alzheimer's-related study in flies---A beta 42 and neuronal transmission

Lin JY, Wang WA, Zhang X, Liu HY, Zhao XL, Huang FD. Intraneuronal accumulation of Aβ42 induces age-dependent slowing of neuronal transmission in Drosophila. Neurosci Bull. 2014 Apr;30(2):185-90. PMID: 24733651.

Drosophila studies & cancer -- three new reports

Two reviews:

Markstein M. Modeling colorectal cancer as a 3-dimensional disease in a dish: the case for drug screening using organoids, zebrafish, and fruit flies. Drug Discov Today Technol. 2013  Spring;10(1):e73-81. PMID: 24050233.  
From the abstract: "This review discusses recent shifts in the understanding of colorectal cancer as a stem cell based disease ... recent advances in the culturing of colorectal stem cells using mammalian organoids, zebrafish, and Drosophila offer promising avenues for anti-CSC drug discovery."

Das TK, Cagan RL. A Drosophila approach to thyroid cancer therapeutics. Drug Discov Today Technol. 2013 Spring;10(1):e65-71. PMID: 24050232; PMCID: PMC3779345.  
From the abstract: "... In this review, we examine the contributions of work in the fruit fly Drosophila toward multiple endocrine neoplasia type 2 (MEN2), a Ret-based disease to which recent Drosophila models have proven useful both for understanding disease mechanism as well as helping identify new generation therapeutics."

And a research resport:

Lourenço FC, Munro J, Brown J, Cordero J, Stefanatos R, Strathdee K, Orange C, Feller SM, Sansom OJ, Vidal M, Murray GI, Olson MF. Reduced LIMK2 expression in colorectal cancer reflects its role in limiting stem cell proliferation. Gut.2014 Mar;63(3):480-93. PMID: 23585469; PMCID: PMC3932979.

From the abstract: "... Genetic analysis in Drosophila midgut and intestinal epithelial cells isolated from genetically modified mice revealed a conserved role for LIMK2 in constraining gastrointestinal stem cell proliferation. ..."

Review--animal models and Oculopharyngeal Muscular Dystrophy

Chartier A, Simonelig M. Animal models in therapeutic drug discovery for oculopharyngeal muscular dystrophy. Drug Discov Today Technol. 2013 Spring;10(1):e103-8. PMID: 24050237.

Fly assays included in Parkinson's related study

Martin I, Kim JW, Lee BD, Kang HC, Xu JC, Jia H, Stankowski J, Kim MS, Zhong J, Kumar M, Andrabi SA, Xiong Y, Dickson DW, Wszolek ZK, Pandey A, Dawson TM, Dawson VL. Ribosomal Protein s15 Phosphorylation Mediates LRRK2 Neurodegeneration in Parkinson's Disease. Cell. 2014 Apr 10;157(2):472-85. PMID: 24725412.

Methods review likely helpful for designing disease-related fly heart studies

Ocorr K, Vogler G, Bodmer R. Methods to assess Drosophila heart development, function and aging. Methods. 2014 Apr 8. pii: S1046-2023(14)00133-9. PMID: 24727147.

Prion protein study includes fly assay

Robinson SW, Nugent ML, Dinsdale D, Steinert JR. Prion protein facilitates synaptic vesicle release by enhancing release probability. Hum Mol Genet. 2014 Apr 9. PMID: 24722203.

Emerging Drosophila model? Aspect of fly trachael system is compared to mammalian blood vessels

Linneweber GA, Jacobson J, Busch KE, Hudry B, Christov CP, Dormann D, Yuan M, Otani T, Knust E, de Bono M, Miguel-Aliaga I. Neuronal control of metabolism through nutrient-dependent modulation of tracheal branching. Cell. 2014 Jan 16;156(1-2):69-83. PMID: 24439370; PMCID: PMC3898607.

Two reports related to neurodegenerative diseases

Hu Y, Han Y, Wang X, Xue L. Aging-related neurodegeneration eliminates male courtship choice in Drosophila. Neurobiol Aging. 2014 Mar 1. pii:S0197-4580(14)00232-2. PMID: 24684795.

Afsari F, Christensen KV, Smith GP, Hentzer M, Nippe OM, Elliott CJ, Wade AR. Abnormal visual gain control in a Parkinson's Disease model. Hum Mol Genet. 2014 Apr 9. PMID: 24718285.

Synapse growth defects in acyl-CoA mutant flies--study with relevance to intellectual disability

Liu Z, Huang Y, Hu W, Huang S, Wang Q, Han J, Zhang YQ. dAcsl, the Drosophila ortholog of acyl-CoA synthetase long-chain family member 3 and 4, inhibits synapse growth by attenuating bone morphogenetic protein signaling via endocytic recycling. J Neurosci. 2014 Feb 19;34(8):2785-96. PMID: 24553921.

From the abstract: "... Mutations in acyl-CoA synthetase long-chain family member 4 (ACSL4), which converts long-chain fatty acids to acyl-CoAs, result in nonsyndromic X-linked mental retardation. ... expression of human ACSL4 rescued the endocytic trafficking and NMJ phenotypes of dAcsl mutants. Together, our results reveal a novel mechanism whereby dAcsl facilitates Rab11-dependent receptor recycling and provide insights into the pathogenesis of ACSL4-related mental retardation."

Inducible fly model of prion disease

Murali A, Maue RA, Dolph PJ. Reversible symptoms and clearance of mutant prion protein in an inducible model of a genetic prion disease in Drosophila melanogaster. Neurobiol Dis. 2014 Mar 28. pii: S0969-9961(14)00074-6. PMID: 24686303.

Flavanoids and A-beta-42

Singh SK, Gaur R, Kumar A, Fatima R, Mishra L, Srikrishna S. The Flavonoid Derivative 2-(4' Benzyloxyphenyl)-3-hydroxy-chromen-4-one Protects Against Aβ(42)-Induced Neurodegeneration in Transgenic Drosophila: Insights from In Silico and In Vivo Studies. Neurotox Res. 2014 Apr 5. PMID: 24706035.

Fly and human studies related to Wolfram syndrome

Jones MA, Amr S, Ferebee A, Huynh P, Rosenfeld JA, Miles MF, Davies AG, Korey CA, Warrick JM, Shiang R, Elsea SH, Girirajan S, Grotewiel M. Genetic studies in Drosophila and humans support a model for the concerted function of CISD2, PPT1 and CLN3 in disease. Biol Open. 2014 Apr 4. pii: bio.20147559v1. PMID: 24705017.

ALS-related fly study includes Drosophila assays

Alami NH, Smith RB, Carrasco MA, Williams LA, Winborn CS, Han SS, Kiskinis E, Winborn B, Freibaum BD, Kanagaraj A, Clare AJ, Badders NM, Bilican B, Chaum E, Chandran S, Shaw CE, Eggan KC, Maniatis T, Taylor JP. Axonal transport of TDP-43 mRNA granules is impaired by ALS-causing mutations. Neuron. 2014 Feb 5;81(3):536-43. PMID: 24507191; PMCID: PMC3939050.

Review of Drosophila as a model for understanding the genetics and neuropathy of intellectual disability

van der Voet M, Nijhof B, Oortveld MA, Schenck A. Drosophila models of early onset cognitive disorders and their clinical applications. Neurosci Biobehav Rev. 2014 Mar 21. pii: S0149-7634(14)00057-8. PMID: 24661984.

From the abstract:  "... The available resources and efficiency of Drosophila place it in a position to tackle the main challenges in the field: mapping functional modules of ID [intellectual disability] genes to provide conceptually novel insights into the genetic control of cognition, tailored functional studies to improve 'next-generation' diagnostics, and identification of reversible ID phenotypes and medication. ... In conclusion, Drosophila provides many opportunities to advance future medical genomics of early onset cognitive disorders"

Cross-species study related to Bardet-Biedl syndrome

Leitch CC, Lodh S, Prieto-Echagüe V, Badano JL, Zaghloul NA. Basal body proteins regulate Notch signaling via endosomal trafficking. J Cell Sci. 2014 Mar 28. PMID: 24681783.

Tissue remodeling & tumors--a review

Patel PH, Edgar BA. Tissue design: how Drosophila tumors remodel their neighborhood. Semin Cell Dev Biol. 2014 Mar 28. PMID: 24685612.

JAK/STAT and tumors--a review

Amoyel M, Anderson AM, Bach EA. JAK/STAT pathway dysregulation in tumors: A Drosophila perspective. Semin Cell Dev Biol. 2014 Mar 28. pii:S1084-9521(14)00059-7. PMID: 24685611.

Receptor tyrosine kinase fly study with "potential implications" for cancer therapeutics

Macagno JP, Diaz Vera J, Yu Y, Macpherson I, Sandilands E, Palmer R, Norman JC, Frame M, Vidal M. FAK Acts as a Suppressor of RTK-MAP Kinase Signalling in Drosophila melanogaster Epithelia and Human Cancer Cells. PLoS Genet. 2014 Mar 27;10(3):e1004262. PMID: 24676055.

From the abstract: "... the FAK-mediated negative regulation of RTK/MAPK signalling described here may have potential implications in the designing of therapy strategies for RTK-driven tumours."

Chaperone-domain protein prevents CNS toxicity in fly model of Alzheimer's Disease

Hermansson E, Schultz S, Crowther D, Linse S, Winblad B, Westermark G, Johansson J, Presto J. The chaperone domain BRICHOS prevents amyloid β-peptide CNS toxicity in Drosophila melanogaster. Dis Model Mech. 2014 Mar 28. PMID: 24682783.

Cholera and Notch signaling--study includes fly assays

Guichard A, Cruz-Moreno B, Aguilar B, van Sorge NM, Kuang J, Kurkciyan AA, Wang Z, Hang S, Pineton de Chambrun GP, McCole DF, Watnick P, Nizet V, Bier E. Cholera toxin disrupts barrier function by inhibiting exocyst-mediated trafficking of host proteins to intestinal cell junctions. Cell Host Microbe. 2013 Sep 11;14(3):294-305. PMID: 24034615; PMCID: PMC3786442.

Effect of a compound found in green tea tests with fly Parkinson's model

Siddique YH, Jyoti S, Naz F. Effect of epicatechin gallate dietary supplementation on transgenic Drosophila model of Parkinson's disease. J Diet Suppl. 2014 Jun;11(2):121-30. PMID: 24670116.

Two studies related to Alzheimer's Disease

Wang X, Kim JR, Lee SB, Kim YJ, Jung MY, Kwon HW, Ahn YJ. Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer's disease Drosophila models. BMC Complement Altern Med. 2014 Mar 5;14(1):88.PMID: 24597901; PMCID: PMC3946151.

Shaw JL, Chang KT. Nebula/DSCR1 upregulation delays neurodegeneration and protects against APP-induced axonal transport defects by restoring calcineurin and GSK-3β signaling. PLoS Genet. 2013;9(9):e1003792. PMID: 24086147; PMCID: PMC3784514.

Suppression of degeneration in a fly model of spinocerebellar ataxia

Cushman-Nick M, Bonini NM, Shorter J. Hsp104 suppresses polyglutamine-induced degeneration post onset in a drosophila MJD/SCA3 model. PLoS Genet. 2013;9(9):e1003781. PMID: 24039611; PMCID: PMC3764203.

Flies, zinc binding, mitochondria and ALS

Bahadorani S, Mukai ST, Rabie J, Beckman JS, Phillips JP, Hilliker AJ. Expression of zinc-deficient human superoxide dismutase in Drosophila neurons produces a locomotor defect linked to mitochondrial dysfunction. Neurobiol Aging. 2013 Oct;34(10):2322-30. PMID: 23601674.

Fly model of myotonic dystrophy type 1

Picchio L, Plantie E, Renaud Y, Poovthumkadavil P, Jagla K. Novel Drosophila model of myotonic dystrophy type 1: phenotypic characterization and genome-wide view of altered gene expression. Hum Mol Genet. 2013 Jul 15;22(14):2795-810. PMID: 23525904.

Drosophila included in vitamin B study

Marzio A, Merigliano C, Gatti M, Vernì F. Sugar and chromosome stability: clastogenic effects of sugars in vitamin b6-deficient cells. PLoS Genet. 2014 Mar 20;10(3):e1004199. PMID: 24651653; PMCID: PMC3961173.

Loss-of-function in flies included in study of inherited cerebral palsy

Kruer MC, Jepperson T, Dutta S, Steiner RD, Cottenie E, Sanford L, Merkens M, Russman BS, Blasco PA, Fan G, Pollock J, Green S, Woltjer RL, Mooney C, Kretzschmar D, Paisán-Ruiz C, Houlden H. Mutations in γ adducin are associated with inherited cerebral palsy. Ann Neurol. 2013 Dec;74(6):805-14. PMID: 23836506; PMCID: PMC3952628.

Patient alleles functionally tested in flies--cancer-related study

Gavilan HS, Kulikauskas RM, Gutmann DH, Fehon RG. In Vivo Functional Analysis of the Human NF2 Tumor Suppressor Gene in Drosophila. PLoS One. 2014 Mar 4;9(3):e90853. PMID: 24595234; PMCID: PMC3942481.

From the abstract:  "... Interestingly, we found that a patient-derived missense allele, NF2L64P, appears to be temperature sensitive. ..."

Fly models, cancer and aneuploidy--a review

Milán M, Clemente-Ruiz M, Dekanty A, Muzzopappa M. Aneuploidy and tumorigenesis in Drosophila. Semin Cell Dev Biol. 2014 Mar 15. pii: S1084-9521(14)00042-1. PMID: 24641887.

Review--flies and study of colorectal cancer

Bell GP, Thompson BJ. Colorectal cancer progression: Lessons from Drosophila? Semin Cell Dev Biol. 2014 Feb 27. pii: S1084-9521(14)00019-6. PMID: 24583474.

Reveiw--model systems in the study of autism spectrum disorders

Doll CA, Broadie K. Impaired activity-dependent neural circuit assembly and refinement in autism spectrum disorder genetic models. Front Cell Neurosci. 2014 Feb 7;8:30. eCollection 2014. Review. PMID: 24570656; PMCID: PMC3916725.

Autophagy and neurodenenerative disease

Bakhoum MF, Bakhoum CY, Ding Z, Carlton SM, Campbell GA, Jackson GR. Evidence for autophagic gridlock in aging and neurodegeneration. Transl Res. 2014 Feb 3. pii: S1931-5244(14)00048-6. PMID: 24561013.

Flies used for signal pathway analysis in cancer-related study

Court H, Amoyel M, Hackman M, Lee KE, Xu R, Miller G, Bar-Sagi D, Bach EA, Bergö MO, Philips MR. Isoprenylcysteine carboxylmethyltransferase deficiency exacerbates KRAS-driven pancreatic neoplasia via Notch suppression. J Clin Invest. 2013 Nov 1;123(11):4681-94. PubMed PMID: 24216479; PubMed Central PMCID: PMC3809775.

Fly cell study identifies conserved host cell factors related to West Nile Virus infection

Yasunaga A, Hanna SL, Li J, Cho H, Rose PP, Spiridigliozzi A, Gold B, Diamond MS, Cherry S. Genome-Wide RNAi Screen Identifies Broadly-Acting Host Factors That Inhibit Arbovirus Infection. PLoS Pathog. 2014 Feb 13;10(2):e1003914. PMID: 24550726; PMCID: PMC3923753.


From the abstract:  "Investigation of two newly identified factors that restrict diverse viruses, dXPO1 and dRUVBL1, in the Tip60 complex, demonstrated they contributed to antiviral defense at the organismal level in adult flies, in mosquito cells, and in mammalian cells. These data suggest the existence of broadly acting and functionally conserved antiviral genes and pathways that restrict virus infections in evolutionarily divergent hosts."

Inducers of hsp70 and prion disease in fly model

Zhang Y, Casas-Tinto S, Rincon-Limas DE, Fernandez-Funez P. Combined pharmacological induction of hsp70 suppresses prion protein neurotoxicity in Drosophila. PLoS One. 2014 Feb 11;9(2):e88522. doi: 10.1371/journal.pone.0088522. PMID: 24523910; PMCID: PMC3921213.

Two fly reports relevant to neurodegenerative diseases

Zhu ZJ, Wu KC, Qian ZM, Yung WH, Ke Y. Drosophila models for studying iron-related neurodegenerative diseases. Sheng Li Xue Bao. 2014 Feb 25;66(1):47-54. PMID: 24553869.

Ling D, Magallanes M, Salvaterra PM. Accumulation of amyloid-like Aβ1-42 in autophagy-endosomal-lysosomal (AEL) vesicles: Potential implications for plaque biogenesis. ASN Neuro. 2014 Feb 12. PMID: 24521233.

Human Rab7 mutations in fly

Janssens K, Goethals S, Atkinson D, Ermanoska B, Fransen E, Jordanova A, Auer-Grumbach M, Asselbergh B, Timmerman V. Human Rab7 mutation mimics features of Charcot-Marie-Tooth neuropathy type 2B in Drosophila. Neurobiol Dis. 2014 Feb 9. PMID: 24521780.

Two reports relevant to intellectual disability

Liu Z, Huang Y, Hu W, Huang S, Wang Q, Han J, Zhang YQ. dAcsl, the Drosophila Ortholog of Acyl-CoA Synthetase Long-Chain Family Member 3 and 4, Inhibits Synapse Growth by Attenuating Bone Morphogenetic Protein Signaling via Endocytic Recycling. J Neurosci. 2014 Feb 19;34(8):2785-2796. PMID: 24553921.

Willemsen MH, Nijhof B, Fenckova M, Nillesen WM, Bongers EM, Castells-Nobau A, Asztalos L, Viragh E, van Bon BW, Tezel E, Veltman JA, Brunner HG, de Vries BB, de Ligt J, Yntema HG, van Bokhoven H, Isidor B, Le Caignec C, Lorino E, Asztalos Z, Koolen DA, Vissers LE, Schenck A, Kleefstra T. GATAD2B loss-of-function mutations cause a recognisable syndrome with intellectual disability and are associated with learning deficits and synaptic undergrowth in Drosophila. J Med Genet. 2013 Aug;50(8):507-14. PMID: 23644463.

Review: Using Drosophila to study organ-to-organ communication in response to a wound

Lee WJ, Miura M. Mechanisms of systemic wound response in Drosophila. Curr Top Dev Biol. 2014;108:153-83. PMID: 24512709.

Review--mice and flies as model systems for studying muscle degeneration

Rai M, Nongthomba U, Grounds MD. Skeletal muscle degeneration and regeneration in mice and flies. Curr Top Dev Biol. 2014;108:247-81. PMID: 24512712.

Two new cancer-related fly studies

Martorell O, Merlos-Suárez A, Campbell K, Barriga FM, Christov CP, Miguel-Aliaga I, Batlle E, Casanova J, Casali A. Conserved mechanisms of tumorigenesis in the Drosophila adult midgut. PLoS One. 2014 Feb 6;9(2):e88413. PMID: 24516653.

Sievers C, Comoglio F, Seimiya M, Merdes G, Paro R. A Deterministic Analysis of Genome Integrity during Neoplastic Growth in Drosophila. PLoS One. 2014 Feb 6;9(2):e87090. PMID: 24516544.

In vivo RNAi fly study relevant to obesity

Baumbach J, Hummel P, Bickmeyer I, Kowalczyk KM, Frank M, Knorr K, Hildebrandt A, Riedel D, Jäckle H, Kühnlein RP. A Drosophila in vivo screen identifies store-operated calcium entry as a key regulator of adiposity. Cell Metab. 2014 PMID: 24506874.

Mini-review on fly models of obesity

Smith WW, Thomas J, Liu J, Li T, Moran TH. From fat fruitfly to human obesity. Physiol Behav. 2014 Feb 5. pii: S0031-9384(14)00034-1. PMID: 24508822.

From patient mutation to model fly: study related to mitochondrial function and disease

van Bon BW, Oortveld MA, Nijtmans LG, Fenckova M, Nijhof B, Besseling J, Vos M, Kramer JM, de Leeuw N, Castells-Nobau A, Asztalos L, Viragh E, Ruiter M, Hofmann F, Eshuis L, Collavin L, Huynen MA, Asztalos Z, Verstreken P, Rodenburg RJ, Smeitink JA, de Vries BB, Schenck A. CEP89 is required for mitochondrial metabolism and neuronal function in man and fly. Hum Mol Genet. 2013 Aug1;22(15):3138-51. PMID: 23575228.

From the abstract: "We identified a homozygous deletion of CEP89 in a patient with isolated complex IV deficiency, intellectual disability and multisystemic problems. ... these data confirm a role for CEP89 in mitochondrial metabolism. In addition, we modeled CEP89 loss of function in Drosophila. ... We conclude that CEP89 proteins play an important role in mitochondrial metabolism, especially complex IV activity, and are required for neuronal and cognitive function across evolution."

Rat cell and fly models related to hereditary spastic paraplegia

Solowska JM, D'Rozario M, Jean DC, Davidson MW, Marenda DR, Baas PW. Pathogenic Mutation of Spastin Has Gain-of-Function Effects on Microtubule Dynamics. J Neurosci. 2014 Jan 29;34(5):1856-67. PMID: 24478365.

Synaptic defects in APP, BACE fly model of Alzheimer's Disease

Mhatre SD, Satyasi V, Killen M, Paddock BE, Moir RD, Saunders AJ, Marenda DR. Altered synapses in a Drosophila model of Alzheimer's disease. Dis Model Mech. 2014 Jan 30. PMID: 24487408.

Fly study with relevance to DiGeorge syndrome

Luhur A, Chawla G, Wu YC, Li J, Sokol NS. Drosha-independent DGCR8/Pasha pathway regulates neuronal morphogenesis. Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1421-6. PMID: 24474768.

Ret and mitochondria in a fly Parkinson's Disease model.

Klein P, Müller-Rischart AK, Motori E, Schönbauer C, Schnorrer F, Winklhofer KF, Klein R. Ret rescues mitochondrial morphology and muscle degeneration of Drosophila Pink1 mutants. EMBO J. 2014 Jan 28. PMID: 24473149.

Endonuclease-G in neurodegenerative disease. Report includes fly studies.

Büttner S, Habernig L, Broeskamp F, Ruli D, Vögtle FN, Vlachos M, Macchi F, Küttner V, Carmona-Gutierrez D, Eisenberg T, Ring J, Markaki M, Taskin AA, Benke S, Ruckenstuhl C, Braun R, Van den Haute C, Bammens T, van der Perren A, Fröhlich KU, Winderickx J, Kroemer G, Baekelandt V, Tavernarakis N, Kovacs GG, Dengjel J, Meisinger C, Sigrist SJ, Madeo F. Endonuclease G mediates α-synuclein cytotoxicity during Parkinson's disease. EMBO J. 2013 Nov 27;32(23):3041-54. PMID: 24129513; PMCID: PMC3844953.

In the above study, results from assays in yeast, C. elegans and Drosophila are combined to help uncover mechanisms underlying cytotoxicity associated with alpha-synuclein.

A comment on this "landmark" study appears in the same journal: Hogg MC and Prehn JH. Endonuclease-G and the pathways to dopaminergic neurodegeneration: a question of location? EMBO J. 2013 Nov 27;32(23):3014-6. PMID: 24162725; PMCID: PMC3844957.