New insights into the noncanonical inflammasome point to caspase-4 as a druggable target.

ABSTRACT: Recent studies indicate that the human lipopolysaccharide sensor caspase-4, unlike its mouse homologue caspase-11, is constitutively expressed and activates pro-IL-18 as well as gasdermin D-mediated pyroptosis. Activation of human caspase-4 causes vascular leakage systemically and at the blood-brain barrier in mice and is implicated in the pathogenesis of a range of inflammatory diseases for which there are currently no effective therapies. These results suggest the therapeutic potential of modulating caspase-4 activity, and structural studies indicate that the caspase-4 exosite might be a promising inhibitory target.

SUBMITTER: Elkayam E 

PROVIDER: S-EPMC12704549 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature