Regulation of the NLRP3 Inflammasome by Post-Translational Modifications and Small Molecules

Abstract

Inflammation is a host protection mechanism that eliminates invasive pathogens from the body. However, chronic inflammation, which occurs repeatedly and continuously over a long period, can directly damage tissues and cause various inflammatory and autoimmune diseases. Pattern recognition receptors (PRRs) respond to exogenous infectious agents called pathogen-associated molecular patterns and endogenous danger signals called danger-associated molecular patterns. Among PRRs, recent advancements in studies of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome have established its significant contribution to the pathology of various inflammatory diseases, including metabolic disorders, immune diseases, cardiovascular diseases, and cancer. The regulation of NLRP3 activation is now considered to be important for the development of potential therapeutic strategies. To this end, there is a need to elucidate the regulatory mechanism of NLRP3 inflammasome activation by multiple signaling pathways, post-translational modifications, and cellular organelles. In this review, we discuss the intracellular signaling events, post-translational modifications, small molecules, and phytochemicals participating in the regulation of NLRP3 inflammasome activation. Understanding how intracellular events and small molecule inhibitors regulate NLRP3 inflammasome activation will provide crucial information for elucidating the associated host defense mechanism and the development of efficient therapeutic strategies for chronic diseases.

Dapagliflozin Restores Impaired Autophagy and Suppresses Inflammation in High Glucose-Treated HK-2 Cells

“…All these studies indicated that the translocation of the NF-κB p65 subunit is crucial for activating inflammation in DKD. On the other hand, the release of IL-1β is controlled by NLRP3 inflammasome activation [22,23,53]. NLRP3 activation may be involved in multiple inflammatory or stress pathways, including NF-κB signaling pathways [23].…”

“…activation [22,23,53]. NLRP3 activation may be involved in multiple inflammatory or stress pathways, including NF-κB signaling pathways [23].…”

“…In addition to proinflammatory cytokines, NF-κB can activate inflammasomes, such as the nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) complex. NLRP3 inflammasome activation involves two signals: the NF-κB translocation-dependent expression of NLRP3 and precursor IL-1β [21,22], and the formation of mature IL-1β, as induced by the NLRP3 inflammasome [22]. These inflammatory cascade processes are crucial for the pathogenesis of DKD [10,23,24].…”

Strategies for Using Muramyl Peptides - Modulators of Innate Immunity of Bacterial Origin - in Medicine

“…Peptidoglycan undergoes structural rearrangements in the process of bacterial growth and division. These autolytic functions are performed by intracellular peptidoglycan hydrolases and amidases, which destroy peptidoglycan and form muramyl peptides (11)(12)(13).…”

Chemical Modulation of the 1-(Piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazole-2-one Scaffold as a Novel NLRP3 Inhibitor

“…However, altered Ca 2+ homeostasis and other ion fluxes (e.g., Na + and Cl − ) have also been implicated in NLRP3 activation [ 15 , 16 ]. Several studies demonstrated that reactive oxygen species (ROS) production, lysosomal destabilization and post-translational modifications are other cellular triggers able to promote the activation and assembly of NLRP3 inflammasome [ 17 , 18 , 19 , 20 , 21 ]. Once activated, NLRP3 undergoes a conformational change and then oligomerizes to give rise to a functional inflammasome, which can trigger the auto-proteolytic cleavage of pro-caspase-1 into the active caspase-1 [ 22 ].…”