Analysis of newly molecular pathogenesis of Parkinson's disease focusing on insolubilization of causal proteins

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15399
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: Gakushuin University
• Principal Investigator: SHIIBA ISSHIN 学習院大学, 理学部, 助教 (30884481)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: パーキンソン病 / Parkin / ミトコンドリア / MITOL

Outline of Final Research Achievements

A pathological feature of Parkinson's disease (PD) is the progressive loss of dopaminergic neurons and decreased dopamine (DA) content in the substantia nigra pars compacta in PD brains. The mechanisms by which parkin, a familial Parkinson’s disease gene product, protects the adult human brain from Parkinson's disease remain incompletely unknown. In this study, we especially focused on insoluble Parkin　as a critical factor inducing neuronal cell death and its protective machinery.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

今回、パーキンソン病の新たな分子病態として、パーキンソン病の原因は不溶性Parkinの蓄積である可能性が示唆されました。また、不溶性Parkinを分解する酵素としてミトコンドリア外膜上に局在するMITOLを同定し、さらに詳細な分解経路も明らかにすることができました。今後、不溶性Parkinの除去を標的とした創薬開発が期待されます。