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Cited by 671Inflammasome and immune disordersImmune Response and InflammationAutoimmune and Inflammatory Disorders Research

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Pharmacological Inhibitors of the NLRP3 Inflammasome

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Zahid, Ayesha, Li, Bofeng, Kombe, Arnaud John Kombe, Jin, Tengchuan, Tao, Jinhui·2019·Frontiers in Immunology
DOI 10.3389/fimmu.2019.02538PMC PMC6842943
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Abstract

Inflammasomes play a crucial role in innate immunity by serving as signaling platforms which deal with a plethora of pathogenic products and cellular products associated with stress and damage. By far, the best studied and most characterized inflammasome is NLRP3 inflammasome, which consists of NLRP3 (nucleotide-binding domain leucine-rich repeat (NLR) and pyrin domain containing receptor 3), ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), and procaspase-1. Activation of NLRP3 inflammasome is mediated by highly diverse stimuli. Upon activation, NLRP3 protein recruits the adapter ASC protein, which recruits the procaspase-1 resulting in its cleavage and activation, inducing the maturation and secretion of inflammatory cytokines and pyroptosis. However, aberrant activation of the NLRP3 inflammasome is implicated in various diseases including diabetes, atherosclerosis, metabolic syndrome, cardiovascular and neurodegenerative diseases; raising a tremendous clinical interest in exploring the potential inhibitors of NLRP3 inflammasome. Recent investigations have disclosed various inhibitors of the NLRP3 inflammasome pathway which were validated through in vitro studies and in vivo experiments in animal models of NLRP3-associated disorders. Some of these inhibitors directly target the NLRP3 protein whereas some are aimed at other components and products of the inflammasome. Direct targeting of NLRP3 protein can be a better choice because it can prevent off target immunosuppressive effects, thus restrain tissue destruction. This paper will review the various pharmacological inhibitors of the NLRP3 inflammasome and will also discuss their mechanism of action.

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Metadata

Authors
Zahid, A., Li, B., Kombe, A. J. K., Jin, T., & Tao, J.
Affiliations
University of Science and Technology of China (CN)
Corresponding author
Jin, Tengchuan
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2019-10-25
Volume
10
Pages
2538-2538
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2019.02538
PMC
PMC6842943
OpenAlex
W2982061867
Cited by
671
References
123
Citations by year
2026: 49 · 2025: 94 · 2024: 107 · 2023: 101 · 2022: 129 · 2021: 122 · 2020: 69
FWCI
7.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (201904a07020103, 81771774)
  • Natural Science Foundation of Anhui Province (1708085MH191)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
Keywords
NLRP3 inflammasome, inflammasome inhibitors, NLRP3, ASC, pyroptosis, inflammatory cytokines, innate immunity, diabetes mellitus, atherosclerosis, metabolic syndrome, neurodegenerative diseases, cardiovascular disease, mechanism of action
MeSH terms
NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Dipeptides, Glyburide, Humans, Nitriles, Sulfones, Inflammasomes, para-Aminobenzoates, ortho-Aminobenzoates

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