The intricate biophysical puzzle of caspase-1 activation

This review takes a closer look at the structural components of the molecules involved in the processes leading to caspase-1 activation.  Interleukins  1β and 18 (IL-1β, IL-18) are well-known  proinflammatory cytokines  that are produced following cleavage of their respective  precursor proteins  by the  cysteine protease  caspase-1. Active caspase-1 is the final step of the  NLRP3 inflammasome , a three-protein intracellular complex involved in inflammation and induction of  pyroptosis  (a proinflammatory cell-death process).  NLRP3  activators facilitate assembly of the  inflammasome  complex and subsequent activation of caspase-1 by autoproteolysis. However, the definitive structural components of active caspase-1 are still unclear and new data add to the complexity of this process. This review outlines the historical and recent findings that provide supporting evidence for the structural aspects of caspase-1 autoproteolysis and activation.