Caspase-gasdermin D pathway

The caspase-gasdermin D pathway is a core component of the pyroptosis cell death program, driven by the cleavage of gasdermin D (GSDMD) by inflammatory caspases (mainly caspase-1, -4, -5 in humans; -1, -11 in mice), usually downstream of inflammasome activation. Upon cleavage, the N-terminal fragment of GSDMD oligomerizes to form large pores in the plasma membrane, resulting in cell swelling, lysis, and release of pro-inflammatory cytokines such as IL-1β and IL-18. This pathway plays a central role in host defense, but aberrant activation is implicated in various inflammatory, infectious, and autoimmune diseases. For structured drug discovery, it is recommended to use precise targets such as "gasdermin D" (GSDMD) or "caspase-1" rather than referring to a pathway name, as drugs act on discrete molecular entities rather than multi-component pathways. The term "Caspase-gasdermin D pathway" should not be used as a canonical target entry.

Other names

Pyroptosis signaling pathwayinflammasome-caspase-gasdermin D axiscaspase-dependent pyroptosis pathway

Inhibition of caspase enzymatic activity to prevent GSDMD cleavage; Direct inhibition of GSDMD pore formation to block pyroptosis