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
Online AccessGet full text
ISSN1663-4365
1663-4365
DOI10.3389/fnagi.2022.879021

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Abstract 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.
AbstractList 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.
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.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.
Author Blevins, Hallie M.
Xu, Yiming
Biby, Savannah
Zhang, Shijun
AuthorAffiliation Department of Medicinal Chemistry, Virginia Commonwealth University , Richmond, VA , United States
AuthorAffiliation_xml – name: Department of Medicinal Chemistry, Virginia Commonwealth University , Richmond, VA , United States
Author_xml – sequence: 1
  givenname: Hallie M.
  surname: Blevins
  fullname: Blevins, Hallie M.
– sequence: 2
  givenname: Yiming
  surname: Xu
  fullname: Xu, Yiming
– sequence: 3
  givenname: Savannah
  surname: Biby
  fullname: Biby, Savannah
– sequence: 4
  givenname: Shijun
  surname: Zhang
  fullname: Zhang, Shijun
BackLink https://www.ncbi.nlm.nih.gov/pubmed/35754962$$D View this record in MEDLINE/PubMed
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Keywords NOD-like receptor
inhibitors
NLRP3
inflammatory diseases
inflammasome
innate immune system
Language English
License Copyright © 2022 Blevins, Xu, Biby and Zhang.
This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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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
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Snippet The NLRP3 inflammasome is a multiprotein complex that plays a pivotal role in regulating the innate immune system and inflammatory signaling. Upon activation...
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SubjectTerms Aging Neuroscience
inflammasome
inflammatory diseases
inhibitors
innate immune system
NLRP3
NOD-like receptor
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Title The NLRP3 Inflammasome Pathway: A Review of Mechanisms and Inhibitors for the Treatment of Inflammatory Diseases
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