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Ku70 alleviates neurodegeneration in drosophila models of Huntington's disease

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Item Type:Article
Title:Ku70 alleviates neurodegeneration in drosophila models of Huntington's disease
Creators Name:Tamura, T. and Sone, M. and Iwatsubo, T. and Tagawa, K. and Wanker, E.E. and Okazawa, H.
Abstract:DNA damage accumulates in genome DNA during the long life of neurons, thus DNA damage repair is indispensable to keep normal functions of neurons. We previously reported that Ku70, a critical molecule for DNA double strand break (DSB) repair, is involved in the pathology of Huntington's disease (HD). Mutant huntingtin (Htt) impaired Ku70 function via direct interaction, and Ku70 supplementation recovered phenotypes of a mouse HD model. In this study, we generate multiple Drosophila HD models that express mutant huntingtin (Htt) in eye or motor neuron by different drivers and show various phenotypes. In such fly models, Ku70 co-expression recovers lifespan, locomotive activity and eye degeneration. In contrast, Ku70 reduction by heterozygous null mutation or siRNA-mediated knock down accelerates lifespan shortening and locomotion disability. These results collectively support that Ku70 is a critical mediator of the HD pathology and a candidate therapeutic target in HD.
Keywords:Animal Disease Models, DNA Damage, DNA-Binding Proteins, Huntington Disease, Locomotion, Microtubule-Associated Proteins, Mutation, Neurons, Nuclear Antigens, Small Interfering RNA, Animals, Drosophila
Source:PLoS ONE
ISSN:1932-6203
Publisher:Public Library of Science (U.S.A.)
Volume:6
Number:11
Page Range:e27408
Date:7 November 2011
Additional Information:Erratum in: PLoS ONE 2012;7(1).
Official Publication:https://doi.org/10.1371/journal.pone.0027408
PubMed:View item in PubMed

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