中国实验动物学报2025，Vol.33Issue(9)：1340-1359,20.DOI:10.3969/j.issn.1005-4847.2025.09.010
α-突触核蛋白致病机制及其疾病模型研究进展
Research progress on the pathogenic mechanisms of α-synuclein and related disease models
摘要
Abstract
The core pathological feature of Parkinson's disease(PD)is the abnormal aggregation of α-synuclein and the result ing neuronal damage.α-Synuclein exhibits toxic effects when it forms oligomers or fibrils,leading to neuronal death via multiple pathways,including mitochondrial dysfunction,impaired vesicular trafficking,dopamine auto-oxidation,and neuroinflammation.In addition,α-synuclein can propagate between cells via exosomes,endocytosis/exocytosis,tunneling nanotubes,or vagal nerve axonal transport,creating a cascade of pathological effects.Animal models of PD that recapitulate the key pathological hallmark of α-synuclein accumulation are indispensable tools for elucidating disease mechanisms and developing novel therapeutic interventions.To date,various strategies,including transgenic techniques,bacterial artificial chromosome(BAC)-mediated expression,viral vector-mediated overexpression,and gene editing,have been employed to develop α-synuclein overexpression animal models.These models have significantly advanced our exploration of the relationship between PD and α-synuclein.This systematic review considers the structure and function of α-synuclein,its mechanisms of toxicity,intercellular propagation pathways,animal models of overexpression,and potential therapeutic targets based on its pathogenic mechanisms.关键词
α-突触核蛋白/寡聚体/多巴胺能神经元/黑质/肠脑轴Key words
α-synuclein/oligomers/dopaminergic neurons/substantia nigra/gut-brain axis分类
生物科学引用本文复制引用
林远东,江娅雯,朱向星,陆春玲,王韬,陈颖珊,唐冬生..α-突触核蛋白致病机制及其疾病模型研究进展[J].中国实验动物学报,2025,33(9):1340-1359,20.基金项目
国家重点研发计划(2021YFA0805901),国家自然科学基金(82070199),广东省基础与应用基础研究基金(2021A1515220078),广西重点研发计划(桂科 AB25069009).Funded by National Key Research and Development Program(2021YFA0805901),National Natural Science Foundation of China(82070199),Guangdong Provincial Basic and Applied Basic Research Foundation(2021A1515220078),Guangxi Key Research and Development Program(guike AB25069009). （2021YFA0805901）
