Cuproptosis as a regulator in human diseases: From basic mechanisms to clinical relevance

Abstract

Cuproptosis is a novel, copper-dependent regulated cell death (RCD) pathway identified in 2022. It is distinct from other forms of cell death, such as ferroptosis, due to its unique mechanism involving mitochondrial copper overload, aggregation of lipoylated TCA-cycle proteins, and subsequent proteotoxic stress. Although secondary reactive oxygen species (ROS) production may occur, cuproptosis is not driven by lipid peroxidation, highlighting its specificity. The significance of cuproptosis extends beyond cancer, notably to neurodegenerative disorders such as Alzheimer's disease (AD), where copper dyshomeostasis exacerbates pathology. In oncology, cuproptosis induction has emerged as a promising therapeutic strategy, with agents including copper ionophores, nanomaterials, and repurposed drugs showing efficacy. This review highlights the molecular uniqueness of cuproptosis, its clinical relevance, and translational challenges in therapeutic applications.

Keywords: Alzheimer's disease; Cancer; Copper chelate; Cuproptosis in therapy; Parkinson's disease; Regulated cell death; Wilson's disease.