Role of necroptosis in spinal cord injury and its therapeutic implications

Spinal cord injury (SCI), a complex neurological disorder, triggers a series of devastating neuropathological events such as ischemia, oxidative stress, inflammatory events, neuronal apoptosis, and motor dysfunction. However, the classical necrosome, which consists of receptor-interacting protein (RIP)1, RIP3, and mixed-lineage kinase domain-like protein, is believed to control a novel type of programmed cell death called necroptosis, through tumour necrosis factor-alpha/tumour necrosis factor receptor-1 signalling or other stimuli. Several studies reported that necroptosis plays an important role in neural cell damage, release of intracellular pro-inflammatory factors, lysosomal dysfunction and endoplasmic reticulum stress. Recent research indicates that necroptosis is crucial to the pathophysiology of a number of neurological disorders and SCIs. In our review, we summarize the potential role of programmed cell death regulated by necroptosis in SCI based on its molecular and pathophysiological mechanisms. We also summarize the targets of several necroptosis pathways, which provide a more reliable reference for the treatment of SCI.