线粒体功能障碍与帕金森病关系的研究进展

Progress relating to mitochondria dysfunction and Parkinson disease

帕金森病是一种多因素引发的神经退行性疾病,表现为黑质纹状体致密部多巴胺能神经元退行性病变。越来越多的研究表明,线粒体功能障碍在帕金森病形成过程中起重要作用。线粒体蛋白parkin,PTEN诱导的激酶1和DJ-1通路的变化以及α突触核蛋白的过表达均是引起线粒体功能障碍的主要原因。目前,研究人员正在努力寻找能够改善线粒体功能从而治疗帕金森病的药物,有些药物已进入临床试验阶段。

Parkinson disease（PD） is a heterogeneous neurodegenerative disease,and its motor manifestations are attributable to the degeneration of dopaminergic neurons within the substantia nigra pars compacta,which has increasingly been linked to mitochondrial dysfunction and inhibition of the electron transport chain.Damages mediated by abnormalities of mitochondrial function and an increase of free radicals have been observed in post mortem PD brain,which confirms mitochondrial dysfunction as central to PD pathogenesis.Genetic causes of PD such as PTEN-induced putative kinase 1,parkin and DJ-1 pathways are overlapping and induce mitochondrial dysfunction and oxidative stress.Overexpression of α-synuclein proteins has been found to influence mitochondria function.Thus,targeting mitochondrial function to delay or prevent neuronal death may represent an effective therapeutic strategy for PD.Several attempts have been made in this respect and tested in clinical trials.