Targeting the NOD-, LRR- and Pyrin Domain-Containing Protein 3 (NLRP3) Inflammasome in Psoriasis and Fatigue

Inflammasomes are intracellular, multi-protein signaling complexes of the innate immune system that activate and control inflammatory responses in nucleated cells. Among these inflammasomes, the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome, a cytosolic sensor that modulates inflammatory responses in nucleated cells upon detection of various danger signals and microbial motifs, has been shown to a play a role in a wide range of pathologies and associated symptomatologies, including psoriasis and associated fatigue. Activation of the NLRP3 inflammasome can lead to caspase-1-dependent release of inflammatory cytokines, which potentially act on surrounding cells and may contribute to symptoms of fatigue. In this review, we will present recent developments in NLRP3 inflammasome research as it relates to psoriasis and fatigue, with a focus on the intracellular signaling pathways governing NLRP3 inflammasome regulation and promising pharmacological therapeutics that inhibit NLRP3 inflammasomal pathways.