中国药理学通报2026，Vol.42Issue(3)：411-415,5.DOI:10.12360/CPB202508067
α-突触核蛋白E46K突变加重帕金森病病理进程的研究进展
Research progress on E46K mutation of α-synuclein exacerbating pathological condition of Parkinson's disease
摘要
Abstract
Parkinson's disease(PD)is a neurodegenerative disorder characterized by bradykinesia,tremor and rigidity.The neuropathological features of PD are progressive loss of do-paminergic neurons and abnormal aggregation of α-synuclein(α-syn)to form Lewy bodies.Among the known PD pathogenic gene mutations,the E46K mutation of the α-synuclein SNCA gene has attracted much attention due to its unique pathological mechanism and significant clinical phenotype.Compared with other common mutations(such as A53T,A30P),the E46K mu-tation not only significantly enhances the oligomerization and fi-brosis tendency of α-syn by changing the electrostatic interac-tion and spatial conformation of α-syn,but also promotes the for-mation of more stable β-sheet structure,resulting in more neuro-toxic aggregates.More importantly,E46K mutation carriers show earlier age of onset,faster disease progression,and more severe behavioral disorders.This article systematically summa-rizes the research progress of the unique molecular mechanism and pathological characteristics of E46 Kα-syn mutation in PD,in order to further clarify the pathogenesis and development of PD.关键词
帕金森病/α-突触核蛋白/E46K突变/氧化应激/线粒体功能障碍/发病机制Key words
Parkinson's disease/α-synuclein/E46K muta-tion/oxidative stress/mitochondrial dysfunction/pathogenesis分类
医药卫生引用本文复制引用
张姗姗,彭也,张钊,楚世峰,陈乃宏..α-突触核蛋白E46K突变加重帕金森病病理进程的研究进展[J].中国药理学通报,2026,42(3):411-415,5.基金项目
国家自然科学基金资助项目(No 82130109) （No 82130109）
