2011 Fiscal Year Final Research Report
Pathomechanism of spinocereballar ataxia with axonal neuropathy(SCAN1)-DNA single strand break repair and neurodegeneration
| Project/Area Number |
21591095
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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 | Kagoshima University |
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Principal Investigator |
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| Research Collaborator |
HIRANO Ryuki 鹿児島大学, 医学部・歯学部附属病院, 医員
NAKAMURA Tomonori 鹿児島大学, 大学院・医歯学総合研究科, 大学院生
HASHIGUCHI Akihiro 鹿児島大学, 医学部・歯学部附属病院, 医員
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| Project Period (FY) |
2009 – 2011
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| Keywords | SCAN1 / Tdp1 / SSBR / 末梢神経障害 / 一本鎖DNA修復 / ノックアウトマウス |
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| Research Abstract |
Spinocerebellar ataxia with axonal neuropathy(SCAN1) is an autosomal recessive disorder characterized by ataxia, cerebellar atrophy, and peripheral neuropathy. We found SCAN1 is caused by a specific point mutation the tyrosyl-DNA phosphodiesterase(TDP1) gene. Functional and genetic studies suggest that this mutation, which disrupts the active site of the Tdp1 enzyme, causes disease by a combination of decreased catalytic activity and stabilization of the normally transient covalent Tdp1-DNA intermediate. The Tdp1 knockout mice showed the retinitis pigmentosa like phenotype. The RNA expressions were mostly normal in the microarray studies of Tdp1 knockout mice. These findings make spurred understanding of DNA repair in human biology and suggested a novel mechanism of human disease.
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[Journal Article] A new phenotype of mitochondrial disease characterized by familial late-onset predominant axial myopathy and encephalopathy2011
Author(s)
Sakiyama Y, Okamoto Y, Higuchi I, Inamori Y, Sangatsuda Y, Michizono K, Watanabe O, Hatakeyama H, Goto YI, Arimura K, Takashima H.
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Journal Title
Acta Neuropathol
Volume: 121(6)
Pages: 775-783
Peer Reviewed
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