The mechanism of cytotoxicity from ALS-linked Profilin 1 mutations

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18370
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: TANAKA Yoshinori 公益財団法人東京都医学総合研究所, 認知症・高次脳機能研究分野, 研究員 (00747933)
• Co-Investigator(Renkei-kenkyūsha): HASEGAWA Masato 公益財団法人東京都医学総合研究所, 認知症高次脳機能研究分野, 分野長 (10251232) ; NONAKA Takashi 公益財団法人東京都医学総合研究所, 認知症高次脳機能研究分野, 副参事研究員 (30356258) ; KAMETANI Fuyuki 公益財団法人東京都医学総合研究所, 認知症高次脳機能研究分野, 主席研究員 (70186013) ; SUZUKI Genjiro 公益財団法人東京都医学総合研究所, 認知症高次脳機能研究分野, 主席研究員 (60466034) ; HOSOKAWA Masato 公益財団法人東京都医学総合研究所, 認知症高次脳機能研究分野, 主席研究員 (00435116)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: Profilin1 / TDP-43 / ALS / mutation / aggresome / LC3 / seeding / prion

Outline of Final Research Achievements

The nuclear protein TDP-43 accumulates at the cytoplasm of motor neurons, as a pathological form, in the patients of amyotrophic lateral sclerosis (ALS). As the role of TDP-43 in the nucleus is essential, the accumulation of pathological TDP-43 is identified as a cause of ALS. In the present study, we investigated the effect of ALS-linked PFN1 gene mutations, a cause of familial ALS characteristic of TDP-43 accumulation, on the accumulation of TDP-43 using cultured cells. The cells expressing mutant PFN1 harbored PFN1 aggregates, and those sequestered TDP-43. Furthermore, TDP-43 sequestered into PFN1 aggregates was partly converted into the pathological form of TDP-43 that promotes TDP-43 accumulation like a pathological prion.

Free Research Field

分子神経病理学