The NLRP3 Inflammasome Pathway: A Review of Mechanisms and Inhibitors for the Treatment of Inflammatory Diseases

The NLRP3 inflammasome is a multiprotein complex that plays a pivotal role in regulating the innate immune system and inflammatory signaling. Upon activation by PAMPs and DAMPs, NLRP3 oligomerizes and activates caspase-1 which initiates the processing and release of pro-inflammatory cytokines IL-1β...

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Published inFrontiers in aging neuroscience Vol. 14; p. 879021
Main Authors Blevins, Hallie M., Xu, Yiming, Biby, Savannah, Zhang, Shijun
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 10.06.2022
Subjects
Aging Neuroscience
inflammasome
inflammatory diseases
inhibitors
innate immune system
NLRP3
NOD-like receptor
NOD-like receptor
inhibitors
NLRP3
inflammatory diseases
inflammasome
innate immune system
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ISSN1663-4365
1663-4365
DOI10.3389/fnagi.2022.879021

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Summary:The NLRP3 inflammasome is a multiprotein complex that plays a pivotal role in regulating the innate immune system and inflammatory signaling. Upon activation by PAMPs and DAMPs, NLRP3 oligomerizes and activates caspase-1 which initiates the processing and release of pro-inflammatory cytokines IL-1β and IL-18. NLRP3 is the most extensively studied inflammasome to date due to its array of activators and aberrant activation in several inflammatory diseases. Studies using small molecules and biologics targeting the NLRP3 inflammasome pathway have shown positive outcomes in treating various disease pathologies by blocking chronic inflammation. In this review, we discuss the recent advances in understanding the NLRP3 mechanism, its role in disease pathology, and provide a broad review of therapeutics discovered to target the NLRP3 pathway and their challenges.
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Specialty section: This article was submitted to Alzheimer’s Disease and Related Dementias, a section of the journal Frontiers in Aging Neuroscience
Edited by: Evandro Fei Fang, University of Oslo, Norway
Reviewed by: Yinxia Chao, National Neuroscience Institute (NNI), Singapore; Swati Sudhakar More, University of Minnesota Twin Cities, United States
ISSN:1663-4365
1663-4365
DOI:10.3389/fnagi.2022.879021