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多巴胺代谢异常在帕金森病相关病理变化中的作用

王晓蕊, 朱松鑫, 温晓鸣, 谢俊霞, 宋宁^*

青岛大学基础医学院生理学与病理生理学系，脑科学与疾病研究院，青岛 266071

摘要

帕金森病(Parkinson’s disease, PD)是常见的中枢神经系统退行性疾病之一，其主要病理学特征是中脑黑质部的多巴胺(dopamine, DA)能神经元选择性丢失。虽然已发现基因易感性、衰老、环境毒素等因素与PD发病有关，但导致DA能神经元退行性死亡的细胞分子机制仍不明确。DA代谢是DA能神经元中的重要生理过程，其过程与黑质DA能神经元丢失密切相关，DA代谢异常参与了PD神经元变性相关的诸多病理学过程，例如铁代谢异常、α-突触核蛋白异常聚集、内质网应激、蛋白质降解功能障碍、神经炎症反应等。本文就DA代谢异常在PD相关病理学过程中的作用进行综述。

关键词： 多巴胺; 帕金森病; 铁; α-突触核蛋白

分类号：R338;Q42;R741

Altered dopamine metabolism and its role in pathogenesis of Parkinson’s disease

WANG Xiao-Rui, ZHU Song-Xin, WEN Xiao-Ming, XIE Jun-Xia, SONG Ning^*

Department of Physiology and Pathophysiology, School of Basic Medicine; Institute of Brain Science and Disease, Qingdao University, Qingdao 266071, China

Abstract

Parkinson’s disease (PD), one of the most frequent neurodegenerative disorders, is characterized by the selective loss of dopaminergic neurons in the substantia nigra (SN). Genetic vulnerability, aging, environmental insults are believed to contribute to the pathogenesis of PD. However, the cellular and molecular mechanism of dopaminergic neurons degeneration remains incompletely understood. Dopamine (DA) metabolism is a cardinal physiological process in dopaminergic neurons, which is closely related to the loss of dopaminergic neurons in the SN. DA metabolism takes part in several pathological processes of PD neurodegeneration, such as iron metabolism disturbance, α-synuclein mis-folding, endoplasmic reticulum stress, protein degradation dysfunction, neuroinflammatory response, etc. In this review, we will describe altered DA metabolism and its contributions to PD pathogenesis. 

Key words: Dopamine; Parkinson’s disease; iron; α-synuclein

收稿日期：2020-02-06　　录用日期：2020-05-06

通讯作者：宋宁　　E-mail: ningsong@qdu.edu.cn

DOI: 10.13294/j.aps.2020.0051

引用本文：

王晓蕊, 朱松鑫, 温晓鸣, 谢俊霞, 宋宁. 多巴胺代谢异常在帕金森病相关病理变化中的作用[J]. 生理学报 2021; 73 (1): 89-102.

WANG Xiao-Rui, ZHU Song-Xin, WEN Xiao-Ming, XIE Jun-Xia, SONG Ning. Altered dopamine metabolism and its role in pathogenesis of Parkinson’s disease. Acta Physiol Sin 2021; 73 (1): 89-102 (in Chinese with English abstract).