铜稳态调节机制在认知障碍中的作用探析

doi:10.12114/j.issn.1007-9572.2024.0200

中国全科医学 ›› 2025, Vol. 28 ›› Issue (23): 2941-2949.DOI: 10.12114/j.issn.1007-9572.2024.0200

• 综述与专论 • 上一篇

铜稳态调节机制在认知障碍中的作用探析

周连鹏¹, 李伟峰¹^,²^,^*(), 董新刚¹^,³, 王晓元¹

1．450046　河南省郑州市，河南中医药大学康复医学院
2．450003　河南省郑州市，河南中医药大学第三附属医院
3．451200　河南省郑州市，河南中医药大学第一附属医院

收稿日期:2024-06-10 修回日期:2024-08-10 出版日期:2025-08-15 发布日期:2025-06-17
通讯作者: 李伟峰
作者贡献：
周连鹏提出研究命题，进行文章的构思与撰写；李伟峰负责文章的质量控制及审校，并对文章整体负责；王晓元进行文献的检索与收集；董新刚进行论文修订。
基金资助:
河南省科技发展计划(242102310514); 河南省中医药科学研究专项课题(2024ZY1006); 河南省中医药科学研究专项课题(2024ZY1028); 河南省中医药科学研究专项课题重大专项(2022ZYZD05); 第七批全国名老中医药专家学术经验继承工作项目(豫中医函〔2022〕3号)

Research Progress on the Role of Copper Homeostasis Regulation Mechanism in Cognition Disorder

ZHOU Lianpeng¹, LI Weifeng¹^,²^,^*(), DONG Xingang¹^,³, WANG Xiaoyuan¹

1. Rehabilitation Medicine College, Henan University of Chinese Medicine, Zhengzhou 450046, China
2. The Third Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450003, China
3. The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 451200, China

Received:2024-06-10 Revised:2024-08-10 Published:2025-08-15 Online:2025-06-17
Contact: LI Weifeng

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摘要/Abstract

摘要： 认知障碍常表现为学习、记忆、智力、情感、执行力障碍等一系列脑功能缺损表现，常发生在神经功能疾病、衰老、术后等过程中。目前，认知障碍的发病机制尚不明确，血-脑脊液屏障、氧化应激、自噬、炎症、线粒体以及神经递质均与认知障碍有关。最近研究发现，铜代谢和铜死亡相关的铜稳态对认知功能有调控作用，这可能是认知障碍发生、发展过程中的关键机制。本文从线粒体、胶质细胞、氧化应激、炎症因素、神经递质等角度系统地介绍了铜稳态调控机制在认知障碍中的作用（铜稳态失衡时，铜离子水平紊乱，电解质代谢异常，发生氧化应激、炎症聚集、线粒体紊乱、胶质细胞损伤等一系列反应，甚至诱导神经元发生铜死亡），并对铜稳态在认知障碍中所起的作用进行了总结，以期为认知障碍发病机制提供新的见解，同时也期待为该病的治疗带来新的方案。

关键词: 认知障碍, 铜稳态, 铜代谢, 铜死亡, 综述

Abstract:

Cognitive impairment is often manifested as a series of brain function deficits such as learning, memory, intellectual, emotional, and executive deficits. It often occurs in neurological disorders, aging, and the postoperative period. Currently, the pathogenesis of the disease is unclear, and the blood-brain barrier, oxidative stress, autophagy, inflammation, mitochondria, and neurotransmitters have all been implicated in cognitive dysfunction. Recent studies found that copper homeostasis associated with copper metabolism and copper death had a regulatory role in cognitive function, which may be a key mechanism in the development of cognitive impairment. In this paper, we systematically introduced the role of copper homeostasis regulatory mechanisms in cognitive impairment from the perspectives of mitochondria, glial cells, oxidative reactions, inflammatory factors, neurotransmitters, etc. (When copper homeostasis was imbalanced, copper ion levels were disturbed, electrolyte metabolism was abnormal, and a series of reactions, such as oxidative stress, inflammatory aggregation, mitochondrial disorders, and glial cell damage, occur, and even induce neuronal copper death) and summarised the role of copper homeostasis in cognitive impairment. The role of copper homeostasis in cognitive disorders was summarised, to provide new insights into the pathogenesis of cognitive disorders, as well as bringing new solutions to the treatment of the disease.

Key words: Cognitive impairment, Copper steady state, Copper metabolism, Copper death, Review

中图分类号:

R 741

周连鹏,李伟峰,董新刚,等. 铜稳态调节机制在认知障碍中的作用探析[J]. 中国全科医学, 2025, 28(23): 2941-2949. DOI: 10.12114/j.issn.1007-9572.2024.0200.
ZHOU Lianpeng,LI Weifeng,DONG Xingang, et al. Research Progress on the Role of Copper Homeostasis Regulation Mechanism in Cognition Disorder[J]. Chinese General Practice, 2025, 28(23): 2941-2949. DOI: 10.12114/j.issn.1007-9572.2024.0200.

图/表 3

图1 铜离子在人体内的代谢与调控注：Cu+=一价铜离子，Cu2+=二价铜离子，ATP7A=铜离子转运ATP酶α肽，CTR1=铜转运蛋白1，CCS=超氧化物歧化酶铜伴侣蛋白，SOD1=超氧化物歧化酶1，MT=金属硫蛋白，GSH=谷胱甘肽。

Figure 1 Metabolism and regulation of copper ions in the human body

图2 铜离子在细胞内的调控注: STEAP还原酶=跨膜上皮抗原还原酶，ATOX1=抗氧化蛋白1，TGN=跨高尔基体网络，COX17=细胞色素c氧化酶铜伴侣蛋白17，COX11=细胞色素c氧化酶铜伴侣蛋白11，SCO1=线粒体金属伴侣，CCO=细胞色素C氧化酶。

Figure 2 Intracellular regulation of copper ions

图3 铜死亡及其发生机制注: EC-Cu2+=铜离子载体，Acetyl-CoA=乙酰辅酶A，Citrate=柠檬酸，α-KG=α酮戊二酸，Succinyl-CoA=琥珀酰辅酶A，Oxaloacetate=草酰Z酸，TCA cycle=三羧酸循环，FDX1=铁氧还蛋白1，Fe-S=硫化亚铁，DLAT=二氢硫辛酰胺S-乙酰转移酶，DLST=二氢硫辛酰胺S-琥珀酰转移酶。

Figure 3 Copper death and its mechanism of occurrence

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铜稳态调节机制在认知障碍中的作用探析

Research Progress on the Role of Copper Homeostasis Regulation Mechanism in Cognition Disorder

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