| Project/Area Number |
12670601
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Nagoya University |
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Principal Investigator |
DOYU Manabu Graduate School of Medicine, Nagoya University, Assistant Professor, 大学院・医学研究科, 講師 (90293703)
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| Co-Investigator(Kenkyū-buntansha) |
SOBUE Gen Graduate School of Medicine, Nagoya University, Professor, 大学院・医学研究科, 教授 (20148315)
INUKAI Akira University Hospital, Nagoya University, Assistant Professor, 医学部・附属病院, 助手 (30314016)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | CAG repeat disease / polyglutamine tract / neuronal cell death / Spinal and bulbar muscular atrophy / adenovirus vector / In vitro neuronal cell culture model / DNA chip / Gene expression analysis / アンドロゲン受容体 / ポリグルタミン凝集体 |
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| Research Abstract |
CAG-repeat diseases are inherited neurodegenerative diseases caused by the expansion of CAG repeats in the disease causing genes. The pathogenesis of CAG-repeat diseases remains to be elucidated. In this study, we tried to identify CAG repeat disease-related genes which are involved with neurodegeneration in CAG-repeat diseases. We made in vitro CAG-repeat disease neuronal culture model using adenovirus vectors, which expressed expanded or normal CAG repeat (polyglutamine tract) in human neuroblastoma (SH-SY5Y). This model showed increasing of nuclear aggregates after infection, axonal atrophy and decreasing of cellular activity detected with MTS assay. Further DNA chip analysis (including about 10,000 genes ) revealed upregulation of a gene associated with neurite outgrowth in expanded polyglutamine-expressed group, followed by confirmation with quantitative real time RT-PCR (Taqmann probe PCR). This finding is matched with axonal atrophy observed in CAG-repeat disease animal model.
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