| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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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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