多巴胺能神经元线粒体的氧化损伤与帕金森病  

Mitochondria oxidative injury of dopaminergic neuron in Parkinson's disease

作　　者：王光辉[1] 

机构地区：[1]苏州大学医学部药学院,苏州512123

出　　处：《生命的化学》2014年第2期193-199,共7页Chemistry of Life

基　　金：国家重点基础研究发展计划("973"计划)(2011CB504102);国家自然科学基金项目(31330030)

摘　　要：帕金森病(Parkinson’s disease,PD)的一个主要病理特征就是中脑黑质多巴胺能神经元的丧失,目前研究认为该病理变化与多种因素有关,包括蛋白质异常积聚、泛素蛋白酶体系统功能异常、神经炎症、线粒体损伤和氧化应激。在帕金森病人和动物模型中,中脑黑质有着明显的氧化改变。帕金森病的遗传和环境因素均会作用于线粒体,尤其对线粒体呼吸链复合体I有着抑制作用,造成线粒体损伤,产生活性氧(ROS)。活性氧的大量产生造成脂类、蛋白质和DNA的氧化,从而加剧多巴胺能神经元的线粒体和细胞损伤。多巴胺代谢过程中会产生活性氧,该自身代谢特点决定了多巴胺能神经元存在有较高的氧化应激,易受环境因素的影响。因而,线粒体的氧化损伤在帕金森病病理发生中起着重要作用。Loss of doparminergic neurons in the substantia nigra is the major pathologic character in Parkinson＇s disease （PD）. Multiple events, such as protein aggregation, impairment of the ubiquitin- proteasome pathway, inflammation, mitochondrial dysfunction and oxidative stress, are involved in PD pathogenesis. Abnormal oxidative modifications in the substantia nigra are presented in PD brains as well as animal models. Both genetic and environmental factors in association with PD induce the production of reactive oxygen species （ROS） by inhibiting mitochondrial function, the particular in mitochondrial complex l, resulting in mitochondrial damage. The extensive production of ROS oxidates lipid, protein and DNA, leading to an exaggerating injury of dopaminergic neurons. Moreover, dopaminergic neurons are exposed to oxidative stress because of the production of ROS in the process of dopamine metabolism by themselves. Thus, mitochondria oxidative injury plays an important role in the pathogenesis of PD.

关 键 词：帕金森病 多巴胺能神经元 线粒体 氧化应激 

分 类 号：R742.5[医药卫生—神经病学与精神病学]