Fig. 10.

A proposed schematic of gp120 LAV-mediated NLRP3 inflammasome activation, pyroptosis, neuroinflammation and neuronal death. During HIV-1 infection, gp120 LAV was shed from HIV-1 and/or infected macrophages/microglia. The binding of gp120 LAV to CXCR4 causes both NF-κB activation and K⁺ efflux. NF-κB activation induces the transcription and expression of NLRP3 and pro-IL-1β, and K⁺ efflux triggers NLRP3 inflammasome assembly, caspase-1 activation, pyroptosis and IL-1β release. Microglial pyroptosis further amplifies inflammatory reactions to release IL-1β. Extracellular IL-1β induces microglial activation and the upregulation of neuroinflammatory cytokines and neurotoxic mediators, resulting in neuronal death and dysfunction. MCC950 inhibits microglial NLRP3 inflammasome activation and provides a neuroprotective effect against gp120 LAV-induced neuronal death and dysfunction