An update on the regulatory mechanisms of NLRP3 inflammasome activation

By Seungwha Paik, J. K. Kim, Prashanta Silwal, C. Sasakawa, E. Jo. Cellular & Molecular Immunology, 2021

757 citations recorded by the source corpus.

The NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is a multiprotein complex involved in the release of mature interleukin-1β and 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.

Subfields: Molecular Biology, Nephrology

View Paper: https://www.semanticscholar.org/paper/d3c72c96b350bd3cdc0f6eeaad3b466a34c76e60

Citations in the corpus

• Nanomedicine-Driven Modulation of the Gut–Brain Axis: Innovative Approaches to Managing Chronic Inflammation in Alzheimer’s and Parkinson’s Disease (2025, unknown): “This creates a vicious cycle of uncontrolled inflammation and impaired clearance of toxic aggregates [24].”