| Project/Area Number |
23790982
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurology
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| Research Institution | Niigata University |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 脊髄小脳変性症 / ポリグルタミン病 / 重合体 / 治療 / 治療薬開発 / 小脳機能評価法 |
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| Research Abstract |
Oligomerization of misfolded disease proteins plays a critical role in thepathogenesis of polyglutamine diseases. Increasing evidence suggests that soluble, nonfibrillaroligomers formed early in the pathogenic cascade are more toxic species than insoluble, mature amyloidfibrils or inclusions. To seek novel therapeutic drugs for polyglutamine diseases, we have already donea primary, high-throughput screen using a luciferase-based protein-fragment complementationanalysis (PCA) that can detect polyglutamine protein oligomers in living cells. In this study, weevaluated efficacies of compounds that showed more than 50% suppression of oligomerization in theprimary screen, using the following methods: [1] a fluorescence-based PCA system to directly visualizepolyglutamine protein oligomerization in living cells, and [2] a Caenorhabditis elegans model ofpolyglutamine disease. We found several promising compounds that suppress oligomer formation ofpolyglutamine proteins. We also tried to establish iPS cell lines from skin firoblasts of patients withMachado-Joseph disease [3].
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