2017 Fiscal Year Final Research Report
Neuronal HAP1 functions as a key molecule of intrinsic neuroprotectants in aging and neuropathological conditions
| Project/Area Number |
15K08154
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General anatomy (including histology/embryology)
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
篠田 晃 山口大学, 大学院医学系研究科, 教授 (40192108)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | アポトーシス / 老化 / ミトコンドリア / ハンチントン病 / ノックアウトマウス |
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| Outline of Final Research Achievements |
Huntingtin-associated protein 1 (HAP1) is a core component of the stigmoid body (STB). In this study, we found that subcellular HAP1 morphology was changed from STB formation into cytoplasmic reticulo-granular structure surrounding mitochondria after treatment of proteasome inhibitor (PI) in HAP1-transfected cells. The drug also induced interaction of HAP1 and mitochondrial porin protein VDAC1 on mitochondria. PI-induced apoptosis was shown to be clearly suppressed by over-expression of HAP1 with cytoplasmic reticulo-granular structure in terms of reduction of cytoplasmic cytochrome C release and caspase-3 activation. Rather, PI-induced apoptosis was enhanced in CRISPR-Cas9-mediated Hap1-knock out mice established here. These results indicated that HAP1 is a intrinsic neuroprotectant particularly in proteasome-activity-reduced condition, which is closely related to aged conditions in the brain.
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| Free Research Field |
神経解剖学
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