Fly researchers are very familiar with use of the fly eye to study aspects of diseases such as cancer, Huntington's disease, and even intellectual disability. For this report, researchers used the fly eye in a study related to degeneration of the human retina.
Kmoch S, Majewski J, Ramamurthy V, Cao S, Fahiminiya S, Ren H, MacDonald IM, Lopez I, Sun V, Keser V, Khan A, Stránecký V, Hartmannová H, Přistoupilová A, Hodaňová K, Piherová L, Kuchař L, Baxová A, Chen R, Barsottini OG, Pyle A, Griffin H, Splitt M, Sallum J, Tolmie JL, Sampson JR, Chinnery P; Care4Rare Canada, Banin E, Sharon D, Dutta S, Grebler R, Helfrich-Foerster C, Pedroso JL, Kretzschmar D, Cayouette M, Koenekoop RK. Mutations in PNPLA6 are linked to photoreceptor degeneration and various forms of childhood blindness. Nat Commun. PMID: 25574898; PMCID: PMC4356490.
From the abstract: "Blindness due to retinal degeneration affects millions of people worldwide, but many disease-causing mutations remain unknown. PNPLA6 encodes the patatin-like phospholipase domain containing protein 6, also known as neuropathy target esterase (NTE), which is the target of toxic organophosphates that induce human paralysis due to severe axonopathy of large neurons. ... Here we identify PNPLA6 mutations in childhood blindness in seven families with retinal degeneration ... PNPLA6 localizes mostly at the inner segment plasma membrane in photoreceptors and mutations in Drosophila PNPLA6 lead to photoreceptor cell death. We also report that lysophosphatidylcholine and lysophosphatidic acid levels are elevated in mutant Drosophila. These findings show a role for PNPLA6 in photoreceptor survival and identify phospholipid metabolism as a potential therapeutic target for some forms of blindness."
Tuesday, September 29, 2015
Fly model used to address role of reactive oxygen species in galactosemia
Jumbo-Lucioni PP, Ryan EL, Hopson ML, Bishop HM, Weitner T, Tovmasyan A, Spasojevic I, Batinic-Haberle I, Liang Y, Jones DP, Fridovich-Keil JL. Manganese-based superoxide dismutase mimics modify both acute and long-term outcome severity in a Drosophila melanogaster model of classic galactosemia. Antioxid Redox Signal. 2014 May 20;20(15):2361-71. PMID: 23758052; PMCID: PMC4005492.
More catching up -- fly models helping to reveal new insights into neurodegenertive diseases
Parkinson's Disease
Reviews
Gaki GS, Papavassiliou AG. Oxidative stress-induced signaling pathways implicated in the pathogenesis of Parkinson's disease. Neuromolecular Med. 2014 Jun;16(2):217-30. PMID: 24522549.
Deng H, Yuan L. Genetic variants and animal models in SNCA and Parkinson disease. Ageing Res Rev. 2014 May;15:161-76. PMID: 24768741.
Research reports
Büttner S, Broeskamp F, Sommer C, Markaki M, Habernig L, Alavian-Ghavanini A, Carmona-Gutierrez D, Eisenberg T, Michael E, Kroemer G, Tavernarakis N, Sigrist SJ, Madeo F. Spermidine protects against α-synuclein neurotoxicity. Cell Cycle. 2014;13(24):3903-8. PMID: 25483063.
Siddique YH, Naz F, Jyoti S, Fatima A, Khanam S, Rahul, Ali F, Mujtaba SF, Faisal M. Effect of Centella asiatica Leaf Extract on the Dietary Supplementation in Transgenic Drosophila Model of Parkinson's Disease. Parkinsons Dis. 2014;2014:262058. PMID: 25538856; PMCID: PMC4265550.
Roy B, Jackson GR. Interactions between Tau and α-synuclein augment neurotoxicity in a Drosophila model of Parkinson's disease. Hum Mol Genet. 2014 Jun 1;23(11):3008-23. PMID:
24430504; PMCID: PMC4014195. From the abstract: "Clinical and pathological studies have suggested considerable overlap between tauopathies and synucleinopathies. Several genome-wide association studies have identified alpha-Synuclein (SNCA) and Tau (MAPT) polymorphisms as common risk factors for sporadic Parkinson's disease (PD). However, the mechanisms by which subtle variations in the expression of wild-type SNCA and MAPT influence risk for PD and the underlying cellular events that effect neurotoxicity remain unclear. To examine causes of neurotoxicity associated with the α-Syn/Tau interaction, we used the fruit fly as a model. ... "
Angeles DC, Ho P, Chua LL, Wang C, Yap YW, Ng C, Zhou Zd, Lim KL, Wszolek ZK, Wang HY, Tan EK. Thiol peroxidases ameliorate LRRK2 mutant-induced mitochondrial and dopaminergic neuronal degeneration in Drosophila. Hum Mol Genet. 2014 Jun 15;23(12):3157-65. PMID: 24459295; PMCID: PMC4030771.
Alzheimer's Disease and Tauopathies
Wacker J, Rönicke R, Westermann M, Wulff M, Reymann KG, Dobson CM, Horn U, Crowther DC, Luheshi LM, Fändrich M. Oligomer-targeting with a conformational antibody fragment promotes toxicity in Aβ-expressing flies. Acta Neuropathol Commun. 2014 Apr 11;2:43. PMID: 24725347; PMCID: PMC4029271.
Papanikolopoulou K, Skoulakis EM. Temporally distinct phosphorylations differentiate Tau-dependent learning deficits and premature mortality in Drosophila. Hum Mol Genet. 2015 Apr 1;24(7):2065-77. doi: 10.1093/hmg/ddu726. PMID: 25524708.
Santa-Maria I, Alaniz ME, Renwick N, Cela C, Fulga TA, Van Vactor D, Tuschl T, Clark LN, Shelanski ML, McCabe BD, Crary JF. Dysregulation of microRNA-219 promotes neurodegeneration through post-transcriptional regulation of tau. J Clin Invest. 2015 Feb;125(2):681-6. PubMed PMID: 25574843; PMCID: PMC4319412.
Huntington's Disease
Maheshwari M, Bhutani S, Das A, Mukherjee R, Sharma A, Kino Y, Nukina N, Jana NR. Dexamethasone induces heat shock response and slows down disease progression in mouse and fly models of Huntington's disease. Hum Mol Genet. 2014 May 15;23(10):2737-51. PMID: 24381308.
Lu XH, Mattis VB, Wang N, Al-Ramahi I, van den Berg N, Fratantoni SA, Waldvogel H, Greiner E, Osmand A, Elzein K, Xiao J, Dijkstra S, de Pril R, Vinters HV, Faull R, Signer E, Kwak S, Marugan JJ, Botas J, Fischer DF, Svendsen CN, Munoz-Sanjuan I, Yang XW. Targeting ATM ameliorates mutant Huntingtin toxicity in cell and animal models of Huntington's disease. Sci Transl Med. 2014 Dec 24;6(268):268ra178. PMID: 25540325.
Vittori A, Breda C, Repici M, Orth M, Roos RA, Outeiro TF, Giorgini F, Hollox EJ; REGISTRY investigators of the European Huntington's Disease Network. Copy-number variation of the neuronal glucose transporter gene SLC2A3 and age of onset in Huntington's disease. Hum Mol Genet. 2014 Jun 15;23(12):3129-37. PMID: 24452335; PMCID: PMC4030768.
ALS
King IN, Yartseva V, Salas D, Kumar A, Heidersbach A, Ando DM, Stallings NR, Elliott JL, Srivastava D, Ivey KN. The RNA-binding protein TDP-43 selectively disrupts microRNA-1/206 incorporation into the RNA-induced silencing complex. J Biol Chem. 2014 May 16;289(20):14263-71. PMID: 24719334; PMCID: PMC4022891.
SMA
Rossor AM, Oates EC, Salter HK, Liu Y, Murphy SM, Schule R, Gonzalez MA, Scoto M, Phadke R, Sewry CA, Houlden H, Jordanova A, Tournev I, Chamova T, Litvinenko I, Zuchner S, Herrmann DN, Blake J, Sowden JE, Acsadi G, Rodriguez ML, Menezes MP, Clarke NF, Auer Grumbach M, Bullock SL, Muntoni F, Reilly MM, North KN. Phenotypic and molecular insights into spinal muscular atrophy due to mutations in BICD2. Brain. 2015 Feb;138(Pt 2):293-310. PMID: 25497877; PMCID: PMC4306822.
Additional relevant to neurodegenerative disease
Manayi A, Saeidnia S, Gohari AR, Abdollahi M. Methods for the discovery of new anti-aging products--targeted approaches. Expert Opin Drug Discov. 2014 Apr;9(4):383-405. PMID: 24494592.
Liu L, Zhang K, Sandoval H, Yamamoto S, Jaiswal M, Sanz E, Li Z, Hui J, Graham BH, Quintana A, Bellen HJ. Glial lipid droplets and ROS induced by mitochondrial defects promote neurodegeneration. Cell. 2015 Jan 15;160(1-2):177-90. PMID: 25594180; PMCID: PMC4377295. From the abstract: "Reactive oxygen species (ROS) and mitochondrial defects in neurons are implicated in neurodegenerative disease. Here, we find that a key consequence of ROS and neuronal mitochondrial dysfunction is the accumulation of lipid droplets (LD) in glia. In Drosophila, ROS triggers c-Jun-N-terminal Kinase (JNK) and Sterol Regulatory Element Binding Protein (SREBP) activity in neurons leading to LD accumulation in glia ... "
New fly model of Leigh syndrome
Da-Rè C, von Stockum S, Biscontin A, Millino C, Cisotto P, Zordan MA, Zeviani M, Bernardi P, De Pittà C, Costa R. Leigh syndrome in Drosophila melanogaster: morphological and biochemical characterization of Surf1 post-transcriptional silencing. J Biol Chem. 2014 Oct 17;289(42):29235-46. PMID: 25164807; PMCID: PMC4200275.
From the abstract: "Leigh Syndrome (LS) is the most common early-onset, progressive mitochondrial encephalopathy usually leading to early death. The single most prevalent cause of LS is occurrence of mutations in the SURF1 gene, and LS(Surf1) patients show a ubiquitous and specific decrease in the activity of mitochondrial respiratory chain complex IV (cytochrome c oxidase, COX). SURF1 encodes an inner membrane mitochondrial protein involved in COX assembly. We established a Drosophila melanogaster model of LS based on the post-transcriptional silencing of CG9943, the Drosophila homolog of SURF1. ... We conclude that Surf1 is essential for COX activity and mitochondrial function in D. melanogaster, thus providing a new tool that may help clarify the pathogenic mechanisms of LS."
From the abstract: "Leigh Syndrome (LS) is the most common early-onset, progressive mitochondrial encephalopathy usually leading to early death. The single most prevalent cause of LS is occurrence of mutations in the SURF1 gene, and LS(Surf1) patients show a ubiquitous and specific decrease in the activity of mitochondrial respiratory chain complex IV (cytochrome c oxidase, COX). SURF1 encodes an inner membrane mitochondrial protein involved in COX assembly. We established a Drosophila melanogaster model of LS based on the post-transcriptional silencing of CG9943, the Drosophila homolog of SURF1. ... We conclude that Surf1 is essential for COX activity and mitochondrial function in D. melanogaster, thus providing a new tool that may help clarify the pathogenic mechanisms of LS."
Just a little more human--report describes modification of fly alpha-conotoxin receptor--relevant to neuronal disease modeling
Heghinian MD, Mejia M, Adams DJ, Godenschwege TA, Marí F. Inhibition of cholinergic pathways in Drosophila melanogaster by α-conotoxins. FASEB J. 2015 PMID: 25466886; PMCID: PMC4422358.
FlyRNAi: One-generation in vivo Drosophila genetic screenin...
FlyRNAi: One-generation in vivo Drosophila genetic screenin...: Galindo KA, Endicott TR, Avirneni-Vadlamudi U, Galindo RL. A rapid one-generation genetic screen in a Drosophila model to capture rhabdomyos...
Tech support--Fly as cancer model--Nature Protocols paper on tumor transplants in Drosophila
Rossi F, Gonzalez C. Studying tumor growth in Drosophila using the tissue allograft method. Nat Protoc. 2015 Oct;10(10):1525-34. PMID: 26357008.
From the abstract: "This protocol describes a method to allograft Drosophila larval tissue into adult fly hosts that can be used to assay the tumorigenic potential of mutant tissues. The tissue of interest is dissected, loaded into a fine glass needle and implanted into a host. Upon implantation, nontransformed tissues do not overgrow beyond their normal size, but malignant tumors grow without limit, are invasive and kill the host. ... This method also provides an operational definition of hyperplastic, benign and malignant growth. ..."
See also a post at The Node on this 80-year-old technique:
http://thenode.biologists.com/technique-dating-back-1935-recovered-cancer-research-flies/resources/
From the abstract: "This protocol describes a method to allograft Drosophila larval tissue into adult fly hosts that can be used to assay the tumorigenic potential of mutant tissues. The tissue of interest is dissected, loaded into a fine glass needle and implanted into a host. Upon implantation, nontransformed tissues do not overgrow beyond their normal size, but malignant tumors grow without limit, are invasive and kill the host. ... This method also provides an operational definition of hyperplastic, benign and malignant growth. ..."
See also a post at The Node on this 80-year-old technique:
http://thenode.biologists.com/technique-dating-back-1935-recovered-cancer-research-flies/resources/
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