帕金森病理机制常谈常新:多巴胺能神经的氧化性死亡--ferroptosis和oxytosis  

New Discussion on the Pathological Mechanism of Parkinson's Disease:Oxidative Death of Dopaminergic Neurons-Ferroptosis and Oxytosis

作　　者：段文君 李怡芳[1,2,3] 栗原博[1,2,3] 何蓉蓉[1,2,3] 段金廒 Duan Wenjun;Li Yifang;Li Yuanbo;He Rongrong(Guangdong Engineering Research Center of Chinese Medicine ＆ Disease Susceptibility,Jinan University,Guangzhou 510632,China;Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research,College of Pharmacy,Jinan University,Guangzhou 510632,China;Institute of Traditional Chinese Medicine and Natural Products,Jinan University,Guangzhou 510632,China)

机构地区：[1]暨南大学广东省疾病易感性及中医药研发工程技术研究中心,广州6125052 [2]暨南大学广东省中药药效物质基础和创新药物研究重点实验室,广州6125052 [3]暨南大学药学院,中药及天然药物研究所,广州6125052 [4]不详

出　　处：《世界科学技术-中医药现代化》2018年第6期823-833,共11页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会重大课题(90209003):PMS肝气逆证受体基因表达及其非线性动力学特征;负责人:乔明琦.

摘　　要：黑质致密部多巴胺能神经元的丢失和多巴胺神经递质的释放减少,是临床上导致帕金森病(Parkinson’s disease,PD)的主要病理机制。在基因和环境的共同影响下,存在多种多巴胺能神经元的死亡机制。目前的研究认为凋亡(apoptosis)、坏死(necrosis)和自噬性死亡(autophagic death)都参与了多巴胺能神经元的死亡,但是这些死亡方式还不足以解释其病理进程和机制。铁死亡(ferroptosis)是一种新近发现的铁依赖性程序性细胞死亡途径,其主要特征为铁离子的负荷增多和大量脂质过氧化物的堆积,这些特征与临床上PD病人的大脑分子生物学特征高度吻合。此外,有证据显示ferroptosis和三十年前在神经细胞中发现的氧化凋亡(oxytosis)死亡途径在信号调节等方面具有高度相似性,它们都由氧化应激诱导,可能代表着同种形式的程序性细胞死亡。本综述讨论了目前ferroptosis死亡途径在PD中的研究进展,并简述了关于ferroptosis和oxytosis作为同种细胞死亡方式的可能性。阐明多巴胺能神经元死亡方式及其机制可为抗PD药物的研发提供重要的理论依据。The loss of dopaminergic neurons and the decreased release of dopamine neurotransmitters in the substantia nigra pars compacta are the main pathological mechanisms leading to Parkinson＇s disease （PD） in clinical research. Under the combined influence of genes and environment, there are many death mechanisms of dopaminergic neurons. Current research suggests that apoptosis, necrosis and autophagic death all participate in the death of dopaminergic neurons, but these deaths are not sufficient to explain their pathological processes and mechanisms. Ferroptosis is a newly discovered iron-dependent cell death pathway characterized by increased iron load and accumulation of large amounts of lipid peroxides. These characteristics are highly consistent with the clinical molecular characteristics of the brain in PD patients. In addition, there is evidence that ferroptosis and oxytosis （observed in nerve cells 30 years ago） have a high degree of similarity in signal regulation, and they may represent the same form of programmed cell death. This review discusses the current advances of ferroptosis death pathway in PD, and briefly discusses the possibilities for ferroptosis and oxytosis as the same type of cell death. The elucidation of the death pathway and mechanism of dopaminergic neurons can provide a fundamental theoretical basis for the development of anti-PD drugs.

关 键 词：帕金森病 Α-突触核蛋白 铁死亡脂质过氧化氧化凋亡 

分 类 号：R277.7[医药卫生—中医学]