2012 Fiscal Year Final Research Report
Elucidation of the pathogenesis of spinocerebellar ataxia type 6 using a novel knock-in mouse model that develops Purkinje cell degeneration.
| Project/Area Number |
22590924
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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 | Tokyo Medical and Dental University |
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Principal Investigator |
WATASE Kei 東京医科歯科大学, 脳統合機能研究センター, 准教授 (30376800)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 神経分子病態学 / 神経変性 |
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| Research Abstract |
In order to clarify the molecular pathogenesis of spinocerebellar ataxia type 6 (SCA6), we analyzed a novel knock-in mouse model that faithfully recapitulated many features of SCA6, including Purkinje cell degeneration. Our analysis revealed the lysosomal localization of accumulated mutant Ca_v2.1 channels. The polyQ expansion did not affect the basic properties of the channel even in the early stage of the disease. The lack of cathepsin B, a major lysosomal proteinase, exacerbated the loss of Purkinje cells and was accompanied by an acceleration of inclusion formation. Thus, the pathogenic mechanism of SCA6 involves the endolysosomal degradation pathway
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[Journal Article] Development of Purkinje cell degeneration in a knockin mouse model reveals lysosomal involvement in the pathogenesis of SCA6.2012
Author(s)
Unno, T., Wakamori, M., Koike, M., Uchiyama, Y., Ishikawa, K., Kubota, H., Yoshida, T., Sasakawa, H., Peters, C., Mizusawa, H. and Watase K
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Journal Title
Proc. Natl. Acad. Sci. USA
Volume: 109(43)
Pages: 17693-17698
DOI
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