The Forgotten Inflammasomes: Aim2, Nlrp1, and Nlrc4 in Spinal Cord Injury and Neuroinflammation Publisher



Darabniya A
Source: Inflammopharmacology Published:2025

Abstract

Spinal cord injury (SCI) triggers a cascade of secondary events, among which neuroinflammation plays a central role in driving tissue damage and functional deficits. Inflammasomes are multiprotein complexes that sense cellular stress and mediate caspase-1 activation, interleukin (IL)-1β and IL-18 maturation, and pyroptotic cell death. While the NLRP3 inflammasome has been extensively studied in SCI, emerging evidence suggests that other inflammasomes, including NLRP1, AIM2, and NLRC4, may also contribute to the neuroinflammatory process. This review summarizes current knowledge on non-NLRP3 inflammasomes in SCI, highlighting their distinct activators, cellular distributions, and possible roles in secondary injury. NLRP1 has been implicated in neuronal pyroptosis and axonal degeneration, AIM2 may link mitochondrial and nuclear DNA damage to microglial activation, and NLRC4 has been associated with macrophage- and microglia-driven inflammatory responses. Although evidence remains limited compared to NLRP3, these inflammasomes represent potential contributors to SCI pathology and may serve as novel therapeutic targets. Further experimental and translational studies are needed to clarify their roles and to evaluate pharmacological strategies aimed at modulating their activity. © 2025 Elsevier B.V., All rights reserved.