Role and mechanisms of cuproptosis in the pathogenesis of Wilson's disease (Review)

铜细胞死亡在威尔逊病发病机制中的作用和机制(综述)

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Abstract

Copper, an indispensable trace element in living organisms, plays a pivotal role in human physiological processes. Wilson's disease (WD), an inherited disorder of copper metabolism, is caused by mutations in the ATP7B gene. This genetic malfunction disrupts the dynamics of copper transport and metabolism, thereby impairing ceruloplasmin synthesis and copper excretion. The resultant accumulation of copper in various tissues and organs precipitates a cascade of cellular demise and functional impairment. Notably, cuproptosis, a recently discovered copper‑dependent regulated cell death mechanism, distinctly deviates from conventional cell death paradigms. This novel mode of cell death involves the interaction of copper with lipoacylated proteins within the tricarboxylic acid cycle, leading to proteinotoxic stress and culminating in cell death. In the realm of pathophysiology, cuproptosis has emerged as a pivotal player in a spectrum of diseases, with WD standing as a paradigm closely intertwined with the dysregulation of copper metabolism. This study aimed to encapsulate the pivotal molecular underpinnings of cuproptosis and delve into its crucial involvement in the etiopathogenesis of WD. By elucidating these mechanisms, the present analysis contributes significantly to the nuanced understanding of the pathological underpinnings of WD, thereby providing fresh insights and evidence that may direct innovative therapeutic strategies for this condition.

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