Ku70 alleviates neurodegeneration in Drosophila models of Huntington's disease.
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3210167?pdf=render |
| _version_ | 1828366196016152576 |
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| author | Takuya Tamura Masaki Sone Takeshi Iwatsubo Kazuhiko Tagawa Erich E Wanker Hitoshi Okazawa |
| author_facet | Takuya Tamura Masaki Sone Takeshi Iwatsubo Kazuhiko Tagawa Erich E Wanker Hitoshi Okazawa |
| author_sort | Takuya Tamura |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T05:41:58Z |
| format | Article |
| id | doaj.art-4121465975c646bf8bfdccafd140fb6a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T05:41:58Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4121465975c646bf8bfdccafd140fb6a2022-12-22T02:09:25ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01611e2740810.1371/journal.pone.0027408Ku70 alleviates neurodegeneration in Drosophila models of Huntington's disease.Takuya TamuraMasaki SoneTakeshi IwatsuboKazuhiko TagawaErich E WankerHitoshi OkazawaDNA 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.http://europepmc.org/articles/PMC3210167?pdf=render |
| spellingShingle | Takuya Tamura Masaki Sone Takeshi Iwatsubo Kazuhiko Tagawa Erich E Wanker Hitoshi Okazawa Ku70 alleviates neurodegeneration in Drosophila models of Huntington's disease. PLoS ONE |
| title | Ku70 alleviates neurodegeneration in Drosophila models of Huntington's disease. |
| title_full | Ku70 alleviates neurodegeneration in Drosophila models of Huntington's disease. |
| title_fullStr | Ku70 alleviates neurodegeneration in Drosophila models of Huntington's disease. |
| title_full_unstemmed | Ku70 alleviates neurodegeneration in Drosophila models of Huntington's disease. |
| title_short | Ku70 alleviates neurodegeneration in Drosophila models of Huntington's disease. |
| title_sort | ku70 alleviates neurodegeneration in drosophila models of huntington s disease |
| url | http://europepmc.org/articles/PMC3210167?pdf=render |
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