The role of BAG3/HSP70 complex in selective autophagic degradation of alpha-synuclein

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591272
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: WATANABE Yoshihisa 京都府立医科大学, 医学(系)研究科(研究院), 講師 (50363990)
• Co-Investigator(Kenkyū-buntansha): TANAKA Masaki 京都府立医科大学, 医学研究科, 准教授 (80264753)
• Co-Investigator(Renkei-kenkyūsha): TOKUDA Takahiko 京都府立医科大学, 医学研究科, 教授 (80242692)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: α-シヌクレイン / オートファジー分解 / 凝集体形成 / p62

Outline of Final Research Achievements

The aim of this study is to elucidate the degradation and aggregate formation of α-synuclein associated with Parkinson's disease. α-Synuclein fibrils were introduced into cultured cells, and their degradation was examined immunocytochemically. Autophagy-associated proteins were colocalized to these aggregates. Their degradation was inhibited by knockdown of Atg-5. Moreover, the nucleation activity of α-synuclein fibrils was reduced by inhibition of the lysosomal protein cathepsin B, resulting in a decrease in α-synuclein aggregates. These results suggested that the cleavage of α-synuclein fibrils into lysosomes via autophagy and endocytosis was involved in α-synuclein-aggregate formation.

Free Research Field

神経内科学