Advances in ferroptosis and cuproptosis: implications for spinal cord injury

Spinal cord injury (SCI) is characterized by multifaceted pathophysiological cascade encompassing neuron necrosis, inflammatory responses, glial scar deposition, and impediments to axon regeneration. Currently, there are no effective clinical treatments for SCI. Recently, the molecular mechanisms underlying cuproptosis and ferroptosis have emerged as cutting-edge research frontiers in SCI. Their synergistic effects and crosstalk mechanisms in SCI pathogenesis have garnered considerable scholarly attention. Following SCI, the abrupt disruption of the blood-spinal cord barrier results in a substantial influx of copper and iron ions from the systemic circulation into the injury site. This disrupts intracellular metal ion homeostasis and directly triggers both cuproptosis and ferroptosis signaling pathways. Herein, we analyze recent advances in the mechanisms, key genes, signaling pathways, and functional roles of ferroptosis and cuproptosis, as well as their co-regulatory networks and interplay in SCI, with a focus on basic and clinical investigations into targeted signaling pathway therapies for SCI. This study elucidates innovative therapeutic strategies for SCI via the dual regulation of cuproptosis and ferroptosis signaling pathways.