Copper Homeostasis Imbalance and Cuproptosis in Secondary Brain Injury After Intracerebral Hemorrhage

Peijiang Wei; Yanjun Li; Yunsheng Xue; Jianwen Zhi; Bo Ning

doi:10.54097/3gwcct09

Authors

Peijiang Wei
Yanjun Li
Yunsheng Xue
Jianwen Zhi
Bo Ning

DOI:

https://doi.org/10.54097/3gwcct09

Keywords:

Copper Homeostasis, Cuproptosis, Intracerebral Hemorrhage, Secondary Brain Injury

Abstract

With high mortality and disability rates, intracerebral hemorrhage (ICH) impact patients' daily functional abilities. Secondary brain injury following ICH is a critical factor in the loss of daily functionality, involving multiple mechanisms such as blood-brain barrier disruption, brain edema, oxidative stress, mitochondrial dysfunction, and neuroinflammation, and activating various forms of cell death. Cuproptosis, a novel form of copper-dependent cell death, was introduced, which involves copper-dependent mitochondrial metabolic mechanisms. Recent studies have shown that cuproptosis is closely related to the progression and prognosis of ICH. However, the specific role of cuproptosis in ICH remains unclear, highlighting the importance of investigating the mechanisms of cuproptosis in secondary brain injury. This review summarizes the physiological functions of copper, the foundations of copper homeostasis, the mechanisms of cuproptosis, and its pathophysiological role in ICH, with a focus on the roles of neuroinflammation and mitochondrial damage. Finally, we explore future research directions in regulating copper homeostasis and inhibiting cuproptosis, particularly in relation to challenges in drug development, treatment windows, and target selection. Understanding the relationship between copper homeostasis, cuproptosis, and ICH offers new insights for the treatment of ICH and other neurodegenerative diseases.

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