Two recent fly reports related to neurodegenerative diseases

Richards RI, Samaraweera SE, van Eyk CL, O'Keefe LV, Suter CM. RNA pathogenesis via Toll-like receptor-activated inflammation in expanded repeat neurodegenerative diseases. Front Mol Neurosci. 2013 Sep 5;6:25. PMID: 24046729; PMCID: PMC3763583.

Lenz S, Karsten P, Schulz JB, Voigt A. Drosophila as a screening tool to study human neurodegenerative diseases. J Neurochem. 2013 Sep 12. PMID: 24028575.

New fly model--Pantothenate Kinase-Associated Neurodegeneration

Varun P, Hagit T, Uriya B, Sagiv S, Sebastian K. A new in vivo model of pantothenate kinase-associated neurodegeneration reveals a surprising role for transcriptional regulation in pathogenesis. Front Cell Neurosci. 2013 Sep 9;7:146. PMID: 24058333.

"Small organism, big discoveries"--a review and recent neurodegeneration-related studies that include fly models

Debattisti V, Scorrano L. D. melanogaster, mitochondria and neurodegeneration: small model organism, big discoveries. Mol Cell Neurosci. 2013 Jul;55:77-86. PMID: 22940086.

Vashishtha M, Ng CW, Yildirim F, Gipson TA, Kratter IH, Bodai L, Song W, Lau A, Labadorf A, Vogel-Ciernia A, Troncosco J, Ross CA, Bates GP, Krainc D, Sadri-Vakili G, Finkbeiner S, Marsh JL, Housman DE, Fraenkel E, Thompson LM. Targeting H3K4 trimethylation in Huntington disease. Proc Natl Acad Sci U S A. 2013 Aug 6;110(32):E3027-36. PMID: 23872847; PMCID: PMC3740882.

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.

Beharry C, Alaniz ME, Alonso AD. Expression of Alzheimer-Like Pathological Human Tau Induces a Behavioral Motor and Olfactory Learning Deficit in Drosophila Melanogaster. J Alzheimers Dis. PMID: 23948901.

Mason RP, Casu M, Butler N, Breda C, Campesan S, Clapp J, Green EW, Dhulkhed D, Kyriacou CP, Giorgini F. Glutathione peroxidase activity is neuroprotective in models of Huntington's disease. Nat Genet. 2013 Aug 25. PMID: 23974869.

Study uses fly model of Alzheimer's disease

Park SH, Lee S, Hong YK, Hwang S, Lee JH, Bang SM, Kim YK, Koo BS, Lee IS, Cho KS. Suppressive effects of SuHeXiang Wan on amyloid-β42-induced extracellular signal-regulated kinase hyperactivation and glial cell proliferation in a transgenic Drosophila model of Alzheimer's disease. Biol Pharm Bull. 2013;36(3):390-8. PMID: 23238278.

Relevant review--fly models & tauopathies

Cowan CM, Mudher A. Are tau aggregates toxic or protective in tauopathies? Front Neurol. 2013;4:114. PMID: 23964266; PMCID: PMC3741634.

Glaucoma, the unfolded protein response, and the fly--relevant review

Anholt RR, Carbone MA. A molecular mechanism for glaucoma: endoplasmic reticulum stress and the unfolded protein response. Trends Mol Med. 2013 Jul 19. PMID: 23876925.

Includes discussion of a fly model--transgenic expression of myocilin.

Fly disease model used in Huntingtons disease study

Arribat Y, Bonneaud N, Talmat-Amar Y, Layalle S, Parmentier ML, Maschat F. A Huntingtin Peptide Inhibits PolyQ-Huntingtin Associated Defects. PLoS One. 2013 PMID:
23861941; PMCID: PMC3701666.

Integrated approach to spinocerebellar ataxia includes Drosophila genetic screens

Park J, Al-Ramahi I, Tan Q, Mollema N, Diaz-Garcia JR, Gallego-Flores T, Lu HC, Lagalwar S, Duvick L, Kang H, Lee Y, Jafar-Nejad P, Sayegh LS, Richman R, Liu X, Gao Y, Shaw CA, Arthur JS, Orr HT, Westbrook TF, Botas J, Zoghbi HY. RAS-MAPK-MSK1 pathway modulates ataxin 1 protein levels and toxicity in SCA1. Nature. 2013 Jun 20;498(7454):325-31. PMID: 23719381.

From the abstract: "We have developed a strategy to identify therapeutic entry points ... this approach, which integrates parallel cell-based and Drosophila genetic screens, ... revealed that downregulation of several components of the RAS-MAPK-MSK1 pathway decreases ATXN1 levels and suppresses neurodegeneration in Drosophila and mice."

Study includes fly assays relevant to fragile X-associated tremor ataxia syndrome

Todd PK, Oh SY, Krans A, He F, Sellier C, Frazer M, Renoux AJ, Chen KC, Scaglione KM, Basrur V, Elenitoba-Johnson K, Vonsattel JP, Louis ED, Sutton MA, Taylor JP, Mills RE, Charlet-Berguerand N, Paulson HL. CGG repeat-associated translation mediates neurodegeneration in fragile X tremor ataxia syndrome. Neuron. 2013 May 8;78(3):440-55. PMID: 23602499.

From the abstract: "In Drosophila, CGG repeat toxicity is suppressed by eliminating RAN translation and enhanced by increased polyglycine protein production. These studies expand the growing list of nucleotide repeat disorders in which RAN translation occurs and provide evidence that RAN translation contributes to neurodegeneration."

Fly model of Alzheimer's disease is used to explore links to copper homeostasis.

Lang M, Fan Q, Wang L, Zheng Y, Xiao G, Wang X, Wang W, Zhong Y, Zhou B. Inhibition of human high-affinity copper importer Ctr1 orthologous in the nervous system of Drosophila ameliorates Aβ42-induced Alzheimer's disease-like symptoms. Neurobiol Aging. 2013 Nov;34(11):2604-12. PMID: 23827522.

From the abstract:  "These results imply that copper may play a causative role in developing AD ... Early manipulation of brain copper uptake can have a great effect on Aβ pathology."

Fly cells and in vivo assays used in Huntingtons study.

Lu B, Al-Ramahi I, Valencia A, Wang Q, Berenshteyn F, Yang H, Gallego-Flores T, Ichcho S, Lacoste A, Hild M, Difiglia M, Botas J, Palacino J. Identification of NUB1 as a suppressor of mutant Huntington toxicity via enhanced protein clearance. Nat Neurosci. 2013 May;16(5):562-70. PMID: 23525043.

New fly model related to neurodegeneration--DRPLA fly model--linking neurodegeneration with autophagy

Charroux B, Fanto M. The fine line between waste disposal and recycling: DRPLA fly models illustrate the importance of completing the autophagy cycle for rescuing neurodegeneration. Autophagy. 2010 Jul;6(5):667-9. PMID: 20543566.