Elucidation of pathogenic mechanism of Parkinson's disease through analysis of IPAS, a novel substrate of Parkin

2016 Fiscal Year Final Research Report

• Project/Area Number: 26430051
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Torii Satoru 東京医科歯科大学, 難治疾患研究所, プロジェクト講師 (10444001)
• Co-Investigator(Renkei-kenkyūsha): SOGAWA Kazuhiro 東北大学, 生命科学研究科, 教授 (80175421) ; YASUMOTO Kenichi 東北大学, 生命科学研究科, 准教授 (90241629)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: IPAS / PINK1 / Parkin / リン酸化

Outline of Final Research Achievements

In this study, we have shown that IPAS is regulated by the PINK1-Parkin pathway. IPAS was phosphorylated by PINK1 in a CCCP-dependent manner, bound to Parkin and eventually degraded. Furthermore, by analysis using tissues from patients of Parkinson’s disease, expression of IPAS was increased in substantia nigra in midbrain of these patients. In addition, MPTP-induced neuronal cell death in substantia nigra was decreased in IPAS knockout mice. These results suggest that IPAS accumulation induces neuronal cell death, leading to onset of Parkinson’s disease when regulation by PINK1 and Parkin is lost due to mutations.

Free Research Field

分子細胞生物学