Lysophosphatidylcholine binds α-synuclein and prevents its pathological aggregation  

作　　者：Chunyu Zhao Jia Tu Chuchu Wang Wenbin Liu Jinge Gu Yandong Yin Shengnan Zhang Dan Li Jiajie Diao Zheng-Jiang Zhu Cong Liu 

机构地区：[1]Interdisciplinary Research Center on Biology and Chemistry,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 201210,China [2]University of Chinese Academy of Sciences,Beijing 100049,China [3]Bio-X Institutes,Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders,Ministry of Education,Shanghai Jiao Tong University,Shanghai 200030,China [4]Zhangjiang Institute for Advanced Study,Shanghai Jiao Tong University,Shanghai 200040,China [5]Department of Cancer Biology,University of Cincinnati College of Medicine,Cincinnati,OH 45267,USA

出　　处：《National Science Review》2024年第6期112-121,共10页国家科学评论（英文版）

基　　金：supported by the Major State Basic Research Development Program(2019YFE0120600 to C.L.);the National Key R&D Program of China(2018YFA0800902 to Z.J.Z.);the National Natural Science Foundation of China(82188101 and 32171236 to C.L.;92353302 and 32170683 to D.L.);the Science and Technology Commission of Shanghai Municipality(STCSM)(22JC1410400 to C.L.);the Shanghai Pilot Program for Basic Research-Chinese Academy of Sciences,Shanghai Branch(CYJ-SHFY-2022-005 to C.L.);the CAS Project for Young Scientists in Basic Research(YSBR-095 to C.L.);the Shanghai Municipal Science and Technology Major Project(to Z.J.Z.);the Shanghai Basic Research Pioneer Project(to C.L.and Z.J.Z.).

摘　　要：Accumulation of aggregated α-synuclein (α-syn) in Lewy bodies is the pathological hallmark of Parkinson’sdisease (PD). Genetic mutations in lipid metabolism are causative for a subset of patients withParkinsonism. The role of α-syn’s lipid interactions in its function and aggregation is recognized, yet thespecific lipids involved and how lipid metabolism issues trigger α-syn aggregation and neurodegenerationremain unclear. Here, we found that α-syn shows a preference for binding to lysophospholipids (LPLs),particularly targeting lysophosphatidylcholine (LPC) without relying on electrostatic interactions. LPC iscapable of maintaining α-syn in a compact conformation, significantly reducing its propensity to aggregateboth in vitro and within cellular environments. Conversely, a reduction in the production of cellular LPLs isassociated with an increase in α-syn accumulation. Our work underscores the critical role of LPLs inpreserving the natural conformation of α-syn to inhibit improper aggregation, and establishes a potentialconnection between lipid metabolic dysfunction and α-syn aggregation in PD.

关 键 词：Α-SYNUCLEIN Parkinson’s disease LYSOPHOSPHATIDYLCHOLINE AGGREGATION 

分 类 号：R318[医药卫生—生物医学工程]