Mechanisms of Cuproptosis in Spinal Cord Injury Progression Associated with Copper Metabolic Dysregulation

Abstract

This study aims to investigate the role of copper metabolic dysregulation in the progression of spinal cord injury, with a particular focus on the biological effects of cuproptosis. An animal model of spinal cord injury was established to examine the expression levels of SLC31A1 and ATP7B and to evaluate the association between copper metabolism and spinal cord injury. The results demonstrated that disruption of copper homeostasis markedly exacerbated spinal cord injury severity, characterized by enhanced neuronal apoptosis and heightened inflammatory responses. Further analysis revealed that cuproptosis plays a critical role in the pathophysiological process of spinal cord injury, as evidenced by the significant elevation of lipid peroxidation products, a hallmark of this cell-death pathway. SLC31A1 and ATP7B were identified as key regulators of copper metabolism; upregulation of SLC31A1 increased copper influx, while downregulation of ATP7B impaired copper efflux, leading to intracellular copper accumulation and activation of the cuproptosis pathway. The discussion section provides an in-depth analysis of the relationship between copper metabolic dysregulation and cuproptosis, elucidates the molecular mechanisms underlying cuproptosis in spinal cord injury, and examines the regulatory roles of SLC31A1 and ATP7B. These findings offer new insights into the pathological mechanisms of spinal cord injury and provide a theoretical basis for the development of clinical therapeutic strategies.