{"title":"从细胞死亡到神经系统疾病:揭示铜的作用","authors":"Qiqi Gao, Yu Chen, Wei Hu, Tong Lou, Yu Fang, Zhenlang Lin, Wei Lin","doi":"10.1016/j.nbd.2025.107042","DOIUrl":null,"url":null,"abstract":"<div><div>Copper, a transition metal, plays a crucial role in various physiological processes within the human body. Its homeostasis is vital for maintaining normal cellular function and facilitating optimal performance of the nervous system. To regulate this homeostasis, cells employ sophisticated regulatory mechanisms that govern intracellular copper levels, allowing an adequate supply of copper ions to participate in essential biological functions such as mitochondrial energy production, antioxidant defense, and extracellular matrix stability. Cuproptosis, which was first systematically described in 2022 as a novel form of programmed cell death, involves molecular mechanisms characterized by oxidative stress activation, inhibition of the ubiquitin-proteasome system, and aggregation of lipoacylated proteins. This cascade can compromise mitochondrial function and ultimately result in cell death. In this review, we summarize current knowledge regarding copper metabolism, cuproptosis mechanism, copper-associated cell death, and copper-associated neurological diseases. Importantly, we sought to enhance the current understanding of copper's influence on cellular processes and disease states while advancing clinical approaches for treating these conditions.</div></div>","PeriodicalId":19097,"journal":{"name":"Neurobiology of Disease","volume":"214 ","pages":"Article 107042"},"PeriodicalIF":5.6000,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"From cell death to neurological disease: Unraveling the role of copper\",\"authors\":\"Qiqi Gao, Yu Chen, Wei Hu, Tong Lou, Yu Fang, Zhenlang Lin, Wei Lin\",\"doi\":\"10.1016/j.nbd.2025.107042\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Copper, a transition metal, plays a crucial role in various physiological processes within the human body. Its homeostasis is vital for maintaining normal cellular function and facilitating optimal performance of the nervous system. To regulate this homeostasis, cells employ sophisticated regulatory mechanisms that govern intracellular copper levels, allowing an adequate supply of copper ions to participate in essential biological functions such as mitochondrial energy production, antioxidant defense, and extracellular matrix stability. Cuproptosis, which was first systematically described in 2022 as a novel form of programmed cell death, involves molecular mechanisms characterized by oxidative stress activation, inhibition of the ubiquitin-proteasome system, and aggregation of lipoacylated proteins. This cascade can compromise mitochondrial function and ultimately result in cell death. In this review, we summarize current knowledge regarding copper metabolism, cuproptosis mechanism, copper-associated cell death, and copper-associated neurological diseases. Importantly, we sought to enhance the current understanding of copper's influence on cellular processes and disease states while advancing clinical approaches for treating these conditions.</div></div>\",\"PeriodicalId\":19097,\"journal\":{\"name\":\"Neurobiology of Disease\",\"volume\":\"214 \",\"pages\":\"Article 107042\"},\"PeriodicalIF\":5.6000,\"publicationDate\":\"2025-07-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurobiology of Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S096999612500258X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurobiology of Disease","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S096999612500258X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
From cell death to neurological disease: Unraveling the role of copper
Copper, a transition metal, plays a crucial role in various physiological processes within the human body. Its homeostasis is vital for maintaining normal cellular function and facilitating optimal performance of the nervous system. To regulate this homeostasis, cells employ sophisticated regulatory mechanisms that govern intracellular copper levels, allowing an adequate supply of copper ions to participate in essential biological functions such as mitochondrial energy production, antioxidant defense, and extracellular matrix stability. Cuproptosis, which was first systematically described in 2022 as a novel form of programmed cell death, involves molecular mechanisms characterized by oxidative stress activation, inhibition of the ubiquitin-proteasome system, and aggregation of lipoacylated proteins. This cascade can compromise mitochondrial function and ultimately result in cell death. In this review, we summarize current knowledge regarding copper metabolism, cuproptosis mechanism, copper-associated cell death, and copper-associated neurological diseases. Importantly, we sought to enhance the current understanding of copper's influence on cellular processes and disease states while advancing clinical approaches for treating these conditions.
期刊介绍:
Neurobiology of Disease is a major international journal at the interface between basic and clinical neuroscience. The journal provides a forum for the publication of top quality research papers on: molecular and cellular definitions of disease mechanisms, the neural systems and underpinning behavioral disorders, the genetics of inherited neurological and psychiatric diseases, nervous system aging, and findings relevant to the development of new therapies.