铜稳态失调与神经系统疾病研究进展

Research progress of copper homeostasis disorder and nervous system diseases

铜作为一种重要的微量元素参与人体的多种生化反应和生理过程,主要被用作各种金属酶的辅因子,其在体内处于动态平衡中,维持铜稳态对于正常人体来说是必需的。研究表明,铜稳态失调可能参与多种中枢神经系统疾病的发病过程。铜积累可通过结合三羧酸循环的脂酰化成分形成聚合体,引起细胞毒性最终导致细胞死亡,即铜死亡(Cuproptosis),但其在神经系统的作用机制尚不清楚。本文结合近年国内外文献,从铜稳态对多种神经系统疾病的影响进行综述。文献复习发现,多种神经系统疾病如脑卒中、阿尔茨海默病、帕金森病、Menkes病、Wilson病中均存在铜稳态失调,而其中是否发生铜死亡有待商榷,铜螯合剂已被证明可缓解疾病的发生发展。表明铜死亡的发现可能为铜稳态失调相关神经系统疾病带来新的研究思路。

Copper,as an important trace element,participates in various biochemical reactions and physiological processes in the human body and is mainly used as a co-factor of various metal enzymes.It is in dynamic equilibrium in the body,and maintaining copper homeostasis is necessary for a normal human body.Current researches suggest that copper homeostasis disorders may be involved in the pathogenesis of various central nervous system diseases.Copper accumulation can form aggregates by combining with the acylated components of the tricarboxylic acid cycle,causing cytotoxicity and ultimately leading to cell death,known as cuproptosis.However,its mechanism of action in the nervous system is not yet clear.This article reviews the impact of copper homeostasis on various neurological diseases by combining recent domestic and foreign literature.Literature review shows that copper homeostasis disorders exist in various neurological diseases such as stroke,Alzheimer's disease,Parkinson's disease,Menkes disease,and Wilson's disease,and whether copper death occurs remains to be debated.Copper chelators have been shown to alleviate the occurrence and development of diseases.These results suggest that the discovery of cuproptosis may bring new ideas for the research of neurological diseases related to copper homeostasis disorders.