Uncovering the Critical Role of Cuproptosis in Wilson Disease: Insights Into Potential Therapeutic Targets.

ABSTRACT: Wilson disease (WD) is an inherited disorder caused by ATP7B mutations, resulting in toxic copper accumulation primarily in the liver and brain. While copper-induced hepatotoxicity is a hallmark of WD, the mechanisms linking copper overload to liver injury remain unclear. This study aimed to investigate the role of cuproptosis, a copper-dependent form of regulated cell death, in WD pathogenesis and identify key cuproptosis-related genes (CRGs). We utilised ATP7B-/- mice and HepG2 cells to model WD. Liver injury was assessed histologically and biochemically. Transcriptomic analysis identified differentially expressed CRGs, followed by machine learning (LASSO, SVM-RFE) to identify key genes. Functional enrichment and protein validation were performed. Candidate biomarkers were evaluated in W

SUBMITTER: Tang S 

PROVIDER: S-EPMC12613164 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature