α-突触核蛋白及其在帕金森病发病中的可能机制

α-Synuclein and Its Probable Mechanisms in Pathogenesis of Parkinson's Disease

α-突触核蛋白(AS)是Lewy体的重要组成成分。AS基因定位于第4号染色体,其突变型与常染色体显性遗传性帕金森病(PD)的发病密切相关。在PD中,AS出现了折叠错误和排列混乱。AS的聚集能力,特别是在氧化应激状态下,被认为是其病理机制的核心,AS的异常聚集和降解障碍导致蛋白酶的抑制和多巴胺能神经元的死亡。因此,AS致病形式对认识PD的发生有重要意义。

The clinical features of Parkinson＇ s disease（PD） including tremor, rigidity, and bradykinesia were first systematically described by James Parkinson in ＂An Essay on the Shaking Palsy＂. One to two percent of the population that is more than 65 years old has PD. While the majority of the cases appear to be idiopathic; in rare cases, the disease can be inherited in an antosomal dominant fashion. An Italian family that allowed the first such mutation to be identified carried a point mutation （A53T） in the gene encoding α-synuclein. Subsequently, a second PD-linked autosomal dominant mutation in α-synuclein（A30P） was found in a German family; The E46K mutation was found in a Spanish family with autosomal dominant parkinsonism, dementia, and visual hallucinations of variable severity. Recently, other PD-linked mutations in genes encoding parkin,UCH-L1, and D J-1 have been described. The interactions of these gene products with α-synuclein may be important in the pathogenesis of PD. This review will focus on α-synuclein, since it appears to be centrally important in the pathogenic pathway.