Tuesday, August 26, 2014

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 ..."

Thursday, August 14, 2014

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."

Wednesday, August 13, 2014

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."

Thursday, August 7, 2014

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. ..."

Tuesday, August 5, 2014

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.