Membrane lipid peroxidation is involved in the pathogenesis of Parkinson disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07430
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Aichi Gakuin University
• Principal Investigator: Maruyama Wakako 愛知学院大学, 心身科学部, 教授 (20333396)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: パーキンソン病 / 酸化ストレス / alpha-synuclein / オートファジー

Outline of Final Research Achievements

RRecently, the production and the occurrence of abnormal alpha-synuclein (aS) protein is suggested to play a central role in the neurodegeneration in Parkinson disease (PD). aS is known to occur in the neurons interacting with membrane lipid bilayer, but its function is not clear. In human neuroblastoma SH-SY5Y cells overexpressing aS, lysosome activity was found to be reduced and macroautophagy activity was compensatory increased. aS overexpression protected cells from oxidative stress by membrane-composing docosahexaenoic acid (DHA) and aggregated aS was found to be modified by lipid hydroperoxide derived from DHA. aS may function as a scavenger of lipid radicals by adduct formation and as a result, toxic modified aS is continuously produced in the neurons. Decreased activity of macroautophagy in ageing and PD may be responsible for neuronal death by reduced degradation of toxic aS oligomer modified by lipid radicals.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

「老化」は生物に普遍的な生理現象であり、生体内のノイズやゴミが徐々に蓄積されていく経過と考えられる。今回の研究課題では生命活動に伴うノイズである「酸化ストレス」の結果、酸化修飾タンパク質、特に膜脂質由来の脂質ラジカルによるタンパク付加体（ゴミ）が生成され、毒性を発現するメカニズムについてパーキンソン病を中心に検討を行い、成果を得た。本研究成果を発展させ、神経老化のバイオマーカーとしての酸化脂質修飾タンパク質の有用性、及び老化、神経変性疾患に対する栄養学的介入による老化予防法の開発に結びつけることが期待される。