Exploration of therapeutics commonly available for spinocerebellar ataxias caused by various causal genes

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07123
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Kumamoto University
• Principal Investigator: Seki Takahiro 熊本大学, 大学院生命科学研究部(薬), 准教授 (50335650)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 脊髄小脳失調症 / D-Cysteine / プルキンエ細胞 / シャペロン介在性オートファジー

Outline of Final Research Achievements

We investigated the novel candidates of the therapeutics or preventives commonly for spinocerebellar ataxias (SCAs), which are neurodegenerative disease caused by various causal genes. We revealed that D-cysteine, which produces hydrogen sulfide in a cerebellar specific manner, alleviates the aberrant dendritic morphology of primary cultured Purkinje cells caused by the expression of SCA-causing mutant proteins and that long-term treatment of D-cysteine delays the onset of motor impairment in SCA1 model mice. These findings suggest that D-cysteine could be a novel preventive for various types of SCAs.

Free Research Field

神経科学、神経薬理学

Academic Significance and Societal Importance of the Research Achievements

SCAは常染色体優性性の神経変性疾患であり、患者の子供は1/2の確率でSCA原因遺伝子を保有する。しかしながら、SCAの有効な治療法・発症予防法は存在せず、患者の子供は発症しないことを願うことしかできないのが現状である。D-Cysteineは安全性の高いアミノ酸であるため、SCA原因遺伝子保有者が発症前からD-cysteineを慢性的に服用することで、SCAの発症を予防できる可能性が考えられ、社会的意義も大きい。また、D-cysteineは世界初の神経変性疾患予防薬となることも期待でき、学術的意義も大きい。