| Project/Area Number |
23570195
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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 |
Biophysics
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| Research Institution | Osaka Prefecture University |
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Principal Investigator |
ONDA Maki 大阪府立大学, 理学(系)研究科(研究院), 准教授 (60311916)
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| Co-Investigator(Renkei-kenkyūsha) |
TADA Toshiji 大阪府立大学, 理学系研究科, 教授 (70275288)
MIKAMI Bunzo 京都大学, 農学研究科, 教授 (40135611)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | serpin / conformational diseases / dementia / folding / neurodegeneration / drug design / neuroserpin / ovalbumin / serpins / Protein folding / Dementia / Protein Folding / Conformational Diseases / Serpin / 脳神経疾患 / 生物物理 / 蛋白質 / 痴呆 / フォールディング / 神経変性 / コンフォメーション病 |
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| Research Abstract |
The serpinopathies resulting from serpin polymerization include dementia and cirrhosis. Since 2008, the target molecule for the development of the therapeutic agents has changed from the native protein to folding intermediates. In this study, we found three seed compounds for a cure of serpinopathies based on the data obtained by mapping of a refolding intermediate of neuroserpin, analysis of elongation and domain-swapping mechanisms of polymers of neuroserpin and ovalbumin, and a crystal structure of the cleaved form of the pathogenic mutant Ser49Pro of neuroserpin.
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