Molecular mechanisms regulating NLRP3 inflammasome activation

Inflammasomes are multi-protein signaling complexes that trigger the activation of inflammatory caspases and the maturation of interleukin-1β. Among various inflammasome complexes, the NLRP3 inflammasome is best characterized and has been linked with various human autoinflammatory and autoimmune diseases. Thus, the NLRP3 inflammasome may be a promising target for anti-inflammatory therapies. In this review, we summarize the current understanding of the mechanisms by which the NLRP3 inflammasome is activated in the cytosol. We also describe the binding partners of NLRP3 inftammasome complexes activating or inhibiting the inflammasome assembly. Our knowledge of the mechanisms regulating NLRP3 inflammasome signaling and how these influence inflammatory responses offers further insight into potential therapeutic strategies to treat inflammatory diseases associated with dysregulation of the NLRP3 inflammasome,

An update on the regulatory mechanisms of NLRP3 inflammasome activation

The NOD-,LRR-,and pyrin domain-containing protein 3(NLRP3)inflammasome is a multiprotein complex involved in the release of mature interleukin-1βand triggering of pyroptosis,which is of paramount importance in a variety of physiological and pathological conditions.Over the past decade,considerable advances have been made in elucidating the molecular mechanisms underlying the priming/licensing(Signal 1)and assembly(Signal 2)involved in NLRP3 inflammasome activation.Recently,a number of studies have indicated that the priming/licensing step is regulated by complicated mechanisms at both the transcriptional and posttranslational levels.In this review,we discuss the current understanding of the mechanistic details of NLRP3 inflammasome activation with a particular emphasis on protein-protein interactions,posttranslational modifications,and spatiotemporal regulation of the NLRP3 inflammasome machinery.We also present a detailed summary of multiple positive and/or negative regulatory pathways providing upstream signals that culminate in NLRP3 inflammasome complex assembly.A better understanding of the molecular mechanisms underlying NLRP3 inflammasome activation will provide opportunities for the development of methods for the prevention and treatment of NLRP3 inflammasome-related diseases.