Lysosomal PolyQ accumulation as a target for treatment of SCA6

2016 Fiscal Year Final Research Report

• Project/Area Number: 25282241
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Basic / Social brain science
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Watase Kei 東京医科歯科大学, 学内共同利用施設等, 准教授 (30376800)
• Co-Investigator(Kenkyū-buntansha): 水澤 英洋 国立研究開発法人国立精神・神経医療研究センター, 病院, 病院長 (30144091)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 脊髄小脳変性症6型 / プルキンエ細胞 / 神経炎症 / リソソーム / カルシウムチャンネル / ミクログリア / ポリグルタミン

Outline of Final Research Achievements

Spinocerebellar ataxia type 6 (SCA6) is a neurodegenerative disease characterized by a slowly progressive loss of cerebellar Purkinje cell and motor impairments. In SCA6, a protein containing an expanded polyglutamine stretch gradually accumulates in the cerebellar Purkinje cells but the molecular mechanisms leading to neurodegeneration remains largely elusive. In this study, we have shown that neuroinflammation is involved in the pathogenesis of SCA6. More importantly, by modulating the activation of microglial cells in the cerebellum of a faithful mouse model of SCA6, we succeeded in ameliorating their neurodegenerative phenotypes in the early disease phase.

Free Research Field

神経遺伝学