PANoptosis: a new perspective for targeting programmed cell death after spinal cord injury

Spinal cord injury (SCI) is a devastating condition characterized by a complex cascade of secondary injury following an initial mechanical insult. Among the mechanisms of secondary injury, multiple forms of programmed cell death (PCD)-including apoptosis, necroptosis, and pyroptosis-play key roles in tissue degeneration and loss of function. PANoptosis is a recently proposed concept of cell death that integrates the aforementioned three pro-inflammatory PCD pathways into a single process via a multi-protein complex called the PANoptosome. This review summarizes evidence for the involvement of PANoptosis in SCI pathophysiology and discusses intervention strategies targeting PANoptosis. Targeting PANoptosis offers a novel, holistic approach to mitigating secondary injury in SCI. However, its clinical translation remains challenging and requires further studies to validate efficacy and safety. Elucidating the assembly mechanisms of the PANoptosome and identifying critical regulatory molecules will aid in developing combination therapies and biomarkers to improve neuronal survival and functional recovery in patients with SCI.