Copper homeostasis and cuproptosis represent emerging targets for therapeutic intervention in inflammatory diseases

作者：Wenming Yang, Chuqiao Xiao, Jie Zheng, Jie Song, Xiangguang Li · 发表于：Pharmacological Research · 年份：2025 · DOI：10.1016/j.phrs.2025.107988 · 被引用次数：15 · 研究领域：Trace Elements in Health、Pharmacological Effects of Medicinal Plants、Drug Transport and Resistance Mechanisms

Copper homeostasis dysregulation and the ensuing process of cuproptosis have gained considerable attention as potential therapeutic avenues in the management of inflammatory diseases. As a vital trace element, copper is integral to inflammatory responses, influencing oxidative stress, mitochondrial metabolism, and immune epigenetics. Cuproptosis is characterized as a distinctive copper-dependent cell death mechanism, distinguished by the aberrant aggregation of mitochondrial lipoylated proteins, destabilization of iron-sulfur cluster proteins, and morphological changes such as mitochondrial shrinkage and plasma membrane rupture. This distinguishes it from conventional regulated cell death pathways. Key regulatory genes play crucial roles in modulating copper uptake, efflux, and the enzymatic processes associated with the tricarboxylic acid cycle, exhibiting significant dysregulation in inflammatory states. Copper chelators effectively attenuate inflammation by lowering bioavailable copper levels and curbing reactive oxygen species production. Simultaneously, copper ionophores such as disulfiram promote targeted intracellular copper redistribution, although their tissue specificity and safety profiles require further optimization. Novel strategies, including the nuanced modulation of copper chaperones, the development of functionalized nanoscale copper delivery systems, and innovative copper-based photothermal therapies, provide promising avenues for inflammation regulation. F...