Mechanism of effect and therapeutic potential of NLRP3 inflammasome in spinal cord injury.

Abstract

Spinal cord injury (SCI) is a serious and disabling central nervous system injury that can trigger various neuropathological conditions, resulting in neuronal damage and release of various pro-inflammatory mediators, leading to neurological dysfunction. Currently, surgical decompression, drugs and rehabilitation are primarily used to relieve symptoms and improve endogenous repair mechanisms; however, they cannot directly promote nerve regeneration and functional recovery. SCI can be divided into primary and secondary injuries. Secondary injury is key to determining the severity of injury, whereas inflammation and cell death are important pathological mechanisms in the process of secondary SCI. The activation of the inflammasome complex is thought to be a necessary step in neuro-inflammation and a key trigger for neuronal death. The NLRP3 inflammasome is a cytoplasmic multiprotein complex that is considered an important factor in the development of SCI. Once the NLRP3 inflammasome is activated after SCI, NLRP3 nucleates the assembly of an inflammasome, leading to caspase 1-mediated proteolytic activation of the interleukin-1β (IL-1β) family of cytokines, and induces an inflammatory, pyroptotic cell death. Inhibition of inflammasomes can effectively inhibit inflammation and cell death in the body and promote the recovery of nerve function after SCI. Therefore, inhibition of NLRP3 inflammasome activation may be a promising approach for the treatment of SCI. In this review, we describe the current understanding of NLRP3 inflammasome activation in SCI pathogenesis and its subsequent impact on SCI and summarize drugs and other potential inhibitors based on NLRP3 inflammasome regulation. The objective of this study was to emphasize the role of the NLRP3 inflammasome in SCI, and provide a new therapeutic strategy and theoretical basis for targeting the NLRP3 inflammasome as a therapy for SCI.