Research progress on pyroptosis and its effect on the central nervous system

Pyroptosis is an inflammatory and lysis type of programmed cell death. In the canonical pyroptosis signaling pathway, the NLRP3 inflammasome activates inflammatory caspase-1, which then shears cut the executor protein GSDMD. The N domains of GSDMD move to heterogeneous membranes, form pores, and release inflammatory cytokines IL-1β and IL-18, causing cell membrane swelling and rupture. Pyroptosis is mainly regulated by the key proteins in the signaling pathway, including inflammasome, caspase-1, GSDMD, IL-1β, and IL-18, as well as their agonists and inhibitors. Appropriate pyroptosis can improve host defense mechanisms, while excessive pyroptosis would derive pathological effects on central nervous system, leding to neuroinflammatory response, blood-brain barrier damage, and cognitive disfunction.