Fig. 2.

Schematic of the molecular mechanism of pyroptosis. The canonical pathway of pyroptosis is mediated by caspase-1 and GSDMD. Sensor proteins, including NOD-like receptor family pyrin domain-containing protein 1 (NLRP1), NOD-like receptor family pyrin domain-containing protein 3 (NLRP3), NOD-like receptor family caspase recruitment domain (CARD) domain-containing protein 4 (NLRC4), and Absent in melanoma 2 (AIM2), activate inflammasome assembly in response to exogenous or endogenous stimulations. Caspase-1 is activated from pro-caspase 1 by the inflammasome adaptor protein apoptosis-associated speck-like protein containing CARD (ASC). GSDMD is cleaved by active caspase-1, releasing its N-terminus, which contributes to the pore formation of cells. Inflammatory cytokines, IL-1β and IL-18, are also activated by caspase-1 simultaneously. The non-canonical pathway is the activation of caspase-4/5/11 and cleavage of GSDMD when binding with cytosolic lipopolysaccharide (LPS). The caspase-3/GSDME pathway of pyroptosis can occur in chemotherapy. And granzyme/GSDMB pathway is found in lymphocyte-derived pyroptosis. The figure was created with BioRender.com