α-突触核蛋白E46K突变加重帕金森病病理进程的研究进展OA

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.