2013 Fiscal Year Final Research Report
New strategy for the development of drugs to treat serpinopathies based on structural biology
| 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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| Keywords | serpin / conformational diseases / dementia / folding / neurodegeneration / drug design / neuroserpin / ovalbumin |
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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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