Gasdermins in pyroptosis, inflammation, and cancer

Pyroptosis is a type of programmed inflammatory cell death characterized by balloon-like swelling, membrane rupture, and the release of inflammatory cytokines and danger signals. Pyroptosis is directly triggered by activated gasdermins (GSDMs) which bind to membrane phospholipids, oligomerize, and form pores in cell membranes. GSDM activation is mediated by various effector proteases via cleavage of the linker region or post-translational modification to release the active N-terminal fragment in response to a variety of pathogenic or intrinsic danger signals. GSDM-mediated pyroptosis is involved in the pathogenesis of an array of infectious and inflammatory diseases and cancers. This review discusses recent advances related to the physiological and pathological functions of GSDM-mediated pyroptosis, as well as therapeutic strategies targeting pyroptosis.