Elucidation of the molecular pathogenesis of selective degeneration in multisystem proteinopathy and amyotrophic lateral sclerosis.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07897
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Tohoku University
• Principal Investigator: Warita Hitoshi 東北大学, 大学病院, 助教 (30400245)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 多系統蛋白質症 / 筋萎縮性側索硬化症 / 骨格筋 / RNA結合蛋白 / hnRNP

Outline of Final Research Achievements

To elucidate the cell-selective degeneration mechanism in multisystem proteinopathy (MSP) and amyotrophic lateral sclerosis (ALS), we established multiple lines of MSP3 patients-derived pluripotent stem cells (iPSCs). Motor neurons and skeletal muscle cells defferentiated from the MSP3-specific iPSCs and isogenic control cells were subjected to this study. After improving the efficiency of induction and differentiation into skeletal muscle cells and the long-term culture method, a comparative analyses was performed to reveal molecular cell pathology. As a result, we found that hnRNPA1 was localized to the cytoplasm under oxidative stress as a pathological phenotype of skeletal muscle cells.

Free Research Field

神経内科学

Academic Significance and Societal Importance of the Research Achievements

本研究成果をふまえ、スペクトラムを形成しつつある多系統蛋白質症（MSP）－筋萎縮性側索硬化症（ALS）の原因遺伝子変異がもたらす細胞種選択的な変性メカニズムの解明と治療標的分子の発見につなげることで、治療法が未確立のこれら神経変性疾患のみならず、他の運動ニューロン疾患や骨格筋変性疾患の治療法開発にもつながる意義がある。