The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation

By N. Kelley, Devon Jeltema, Yanhui Duan, Yuan He. International Journal of Molecular Sciences, 2019

3,067 citations recorded by the source corpus.

The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of proinflammatory cytokines IL-1β/IL-18 in response to microbial infection and cellular damage. However, the aberrant activation of the NLRP3 inflammasome has been linked with several inflammatory disorders, which include cryopyrin-associated periodic syndromes, Alzheimer’s disease, diabetes, and atherosclerosis. The NLRP3 inflammasome is activated by diverse stimuli, and multiple molecular and cellular events, including ionic flux, mitochondrial dysfunction, and the production of reactive oxygen species, and lysosomal damage have been shown to trigger its activation. How NLRP3 responds to those signaling events and initiates the assembly of the NLRP3 inflammasome is not fully understood. In this review, we summarize our current understanding of the mechanisms of NLRP3 inflammasome activation by multiple signaling events, and its regulation by post-translational modifications and interacting partners of NLRP3.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/e00aca14a0bf550dd3216db53641de7ba521347c

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In Molecular Biology

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Citations in the corpus

• NLRP3 inflammasome activation and cell death (2021, background): “To date, studies have shown that NLRP3 inflammasomes can be activated through three different signaling pathways: canonical NLRP3 inflammasome activation, noncanonical NLRP3 inflammasome activation, and alternative NLRP3 inflammasome activation, also known as one-step NLRP3 inflammasome activation [”
• An update on the regulatory mechanisms of NLRP3 inflammasome activation (2021, background): “Although the supposition remains controversial, mitochondrial dysfunction has been suggested to be closely linked with other signaling pathways, including K efflux or Cl efflux pathways, for activating the NLRP3 inflammasome.(12,17,116,128,130) Several small molecules that target mitochondria lead t”
• Advanced Glycation End Products and Diabetes Mellitus: Mechanisms and Perspectives (2022, background): “The NLRP3 inflammasome in response to cellular stress-signals mediates caspases-1 cleavage and contributes to the maturation and secretion of key inflammatory cytokines IL-1β/IL-18 [60,61].”
• Pattern recognition receptors in health and diseases (2021, background): “In the NLR family, the NLRP3 inflammasome is closely related to the pathophysiology of a variety of inflammatory diseases, so it is usually used as an inhibitor target.(298,304,305) MCC950 is a specific NLRP3 antagonist, which can prevent its activation or maintain its activation state.”