α-突触核蛋白致病机制研究进展

Progress in the pathogenesis of α-synuclein

细胞内错误折叠的α-突触核蛋白(α-synuclein,α-syn)在中枢神经系统及外周神经系统的沉积导致了帕金森病、路易体痴呆及多系统萎缩等突触核蛋白病的发生,而其病理传播机制尚不完全清楚。最近的研究表明具有神经毒性的寡聚体α-syn的细胞间传播是大脑区域之间疾病传播的主要模式。本综述回顾了不同模式的寡聚体α-syn细胞分泌和再摄取的现有证据,包括细胞间直接转移、朊蛋白样传播、外泌体分泌和内吞作用、纳米隧道及小胶质细胞介导作用,以便更详细地了解突触核蛋白病理学在整个大脑中传播的模式,为防止疾病进展的治疗提供新靶点。

Deposition of intracellular misfoldedα-synuclein(α-syn)in the central nervous system and peripheral nervous system leads to Parkinson′s disease,dementia with Lewy body,multiple system atrophy and other synucleinopathies.But the pathological mechanism of the transmission is not fully understood.Recent studies have shown that intercellular transmission of neurotoxic oligomer α-syn is the main mode of disease transmission between brain regions.This article reviews the existing evidence for different modes of cell secretion and uptake of oligomer α-syn,including direct intercellular transmission,prion-like transmission,exosomes and endocytosis,tunneling nanotubes and microglia-mediated,to provide a more detailed understanding of the patterns of synucleinopathy throughout the brain and to provide new targets for the treatment of disease.