RRC ID 60790
Author Tamura T, Sone M, Iwatsubo T, Tagawa K, Wanker EE, Okazawa H.
Title Ku70 alleviates neurodegeneration in Drosophila models of Huntington's disease.
Journal PLoS One
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.
Volume 6(11)
Pages e27408
Published 2011-1-1
DOI 10.1371/journal.pone.0027408
PII PONE-D-11-01134
PMID 22096569
PMC PMC3210167
MeSH Animals Antigens, Nuclear / genetics Antigens, Nuclear / metabolism* DNA Damage DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Disease Models, Animal Drosophila Drosophila Proteins Huntingtin Protein Huntington Disease / genetics Huntington Disease / metabolism* Huntington Disease / therapy* Ku Autoantigen Locomotion / genetics Locomotion / physiology Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / metabolism Mutation Neurons / metabolism Neurons / pathology* RNA, Small Interfering
IF 2.74
Times Cited 20