FIGURE 1.

The three molecular mechanisms of pyroptosis. (1) In the canonical inflammasome pathway, when the recognition of PAMPs and DAMPs by PRRs was activated, different inflammasomes were assembled with the participation of adaptor proteins (such as: ASC) and effector proteins (such as: caspase family). Subsequently, pro-caspase-1 can be recruited by inflammasomes and activated into cleaved-caspase-1. Cleaved-caspase-1 can activate IL-1β. Next, the activated IL-1β can release into the extracellular. GSDMD can be cleaved into GSDMD-N-terminal (GSDMD-NT) with pore forming characteristics, which is the key process leading to pyroptosis. (2) In the non-canonical inflammasome pathway, caspase-4/5/11 can directly respond to LPS and lead to the cleavage of GSDMD. GSDMB can promote caspase-4 activity by directly binding to the CARD domain of caspase-4. (3) In the caspase-3-mediated inflammasome pathway, GSDME can also be cleaved by caspase-3 and lead to pyroptosis.