Autophagy lysosomal dysfunction associate with the pathogenesis of early onset Parkinson's disease.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24390224
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: HATTORI Nobutaka 順天堂大学, 医学部, 教授 (80218510)
• Co-Investigator(Kenkyū-buntansha): SATO Shigeto 順天堂大学, 医学部, 准教授 (00445537)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 遺伝性パーキンソン病 / タンパク質分解 / ミトコンドリア / オートファジー / リソソーム / PINK1 / Parkin / ATP13A2

Outline of Final Research Achievements

In general, the pathology of Parkinson disease(PD) has been implicated in oxidative damage and mitochondrial dysfunction, which are probably induced by both genetic predisposition and environmental factors. Recent discovery of genes associated with the etiology of familial PD has emphasized the role of autophagy lysosomal system.　PINK1, Parkin and ATP13A2 have been identified as the causal genes responsible for hereditary early onset PD. Mechanistic insights into mitochondrial quality control mediated by PINK1 and Parkin have been revealed. In the process of mitochondria degradation (mitophagy), PINK1 dependent phosphorylation of Parkin is essential for accelerating E3 ligase activity of Parkin. On the other hands, ATP13A2 localizes in lysosome and regulates enzyme activity including cathepsin D. Autophagy lysosomal dysfunction may be the common pathogenesis of early onset PD.

Free Research Field

神経学