Identification of neurotoxic alpha-synuclein oligomers in Parkinson's disease and its application to molecular targeted therapy

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09322
• 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: Tokuda Takahiko 京都府立医科大学, 医学(系)研究科(研究院), 教授 (80242692)
• Co-Investigator(Kenkyū-buntansha): 建部 陽嗣 京都府立医科大学, 医学(系)研究科(研究院), 助教 (00637027) ; 渡邊 義久 京都府立医科大学, 医学(系)研究科(研究院), 講師 (50363990) ; 笠井 高士 京都府立医科大学, 医学(系)研究科(研究院), 講師 (70516062)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: α-シヌクレイン / オリゴマー / パーキンソン病 / 脂質 / エクソソーム

Outline of Final Research Achievements

It is known that extracellular α-synuclein (A-syn) oligomers are important as a pathogenic agent in Parkinson’s disease. In this research project, we first analyzed A-syn molecules in human plasma using gel-filtration chromatography. A-syn molecules in plasma were found in fraction with a molecular mass of 60 kDa and ~2,000 kDa. Furthermore, analyses of human plasma using lipid-adsorption columns demonstrated that A-syn molecules associated with lipids exist in the fractions corresponding to HDLs, and co-exist with ApoA1, ApoE, and ApoJ molecules. Some of those HDL-associated A-syn molecules were detected as oligomers. Our studies revealed that A-syn molecules in human plasma are mainly associated with HDL particles, and at least some part of them are oligomerized.

Free Research Field

神経内科学、蛋白化学