Thursday, December 18, 2014

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.

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