- European Journal of Biology
- Vol: 79 Issue: 1
- Caspase-1: Past and Future of this Major Player in Cell Death and Inflammation
Caspase-1: Past and Future of this Major Player in Cell Death and Inflammation
Authors : Elif EREN, Nesrin OZOREN
Pages : 51-61
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Publication Date : 2020-06-17
Article Type : Review
Abstract :Inflammation is a major physiological process required for the detection of pathogens and their elimination from an organism. It is triggered by the innate immune system that gets activated through the recognition of danger- or pathogen-associated molecular patterns by protein complexes called inflammasomes. The activation of inflammasomes does not only eliminate the replicative niche of pathogens by inducing infected cells’ death (called pyroptosis) but also leads to the secretion of proinflammatory cytokines such as Interleukin-1β (IL-1β) and IL-18, which in turn triggers the recruitment of other immune cells to the infection site and mediates communication with neighboring resident cells. The cysteine aspartate protease Caspase-1 is the common effector enzyme of different inflammasomes and is responsible for the maturation of Gasdermin D and IL-1β required for the induction of pyroptosis and the secretion of IL-1β through the Gasdermin D pores. Several gain of function mutations in inflammasome forming receptor proteins including Caspase-1 were associated with severe auto-immune and auto-inflammatory diseases pointing out the necessity of the tight regulation of these complexes. In this review, we focused on Caspase-1 that is at the crossroad of inflammatory cell death and IL-1β secretion. We describe its discovery, Caspase-1 activator signals, its substrates and the inhibitors that have been designed. We also discuss ongoing research that reveals novel unexpected roles for this protease. This review is a good reference not only for the beginners in innate immunity and inflammation but also provides an update on Caspase-1’s biology for more advanced researchers.Keywords : Caspase-1, inflammasomes, pyroptosis, interleukin-1, Gasdermin D