致病性α-synuclein在帕金森病中的神经毒性与传播机制

Neurotoxicity and transmission mechanism of pathogenic α-synuclein in Parkinson’s disease

帕金森病(Parkinson’s disease,PD)是继阿尔兹海默病(Alzheimer’s disease,AD)后的第二大慢性神经退行性疾病,其主要病理特征是由α-突触核蛋白(α-synuclein,α-syn)的错误折叠和聚集导致的黑质多巴胺神经元的损伤与死亡。近期研究表明,腺苷二磷酸核糖(ADP-ribose)聚合酶1(PARP-1)及其催化产物PAR可以加剧α-syn的病理改变,促进α-syn的聚集,同时由病理性α-syn错误折叠形成的聚集体能够通过与lymphocyte-activation gene 3(LAG3)相互作用在相邻神经元细胞之间传播,加速神经元细胞的损伤,导致PD的发生与进行性发展。本文就近年来在α-syn神经毒性与传播机制等方面的研究做一综述。

Parkinson’s Disease(PD)is the second largest chronic neurodegenerative disease after Alzheimer’s disease.Its main pathological characteristics are the damage and death of dopamine neurons in the substantia nigra caused byα-synuclein(α-syn)misfolding and aggregation.Recent studies have shown that adenosine diphosphate(ADP-ribose)polymerase 1(PARP-1)and its catalytic product PARcan aggravate the pathological changes ofα-syn,promote the accumulation ofα-syn,at the same time,aggerates formed by pathological misfolding ofα-syn can spread throuh adjacent neuronal cells by interaction with lymphocyte-activation gene 3(LAG3),and accelerate neuronal cell damage then lead to the occurrence and progressive development of PD.This article reviews the recent studies onα-syn neurotoxicity and transmission mechanisms.