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Review
. 2022 Jun 10:14:879021.
doi: 10.3389/fnagi.2022.879021. eCollection 2022.

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

Hallie M Blevins  1 , Yiming Xu  1 , Savannah Biby  1 , Shijun Zhang  1
Affiliations
Review

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

Hallie M Blevins et al. Front Aging Neurosci. .

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.

Keywords: NLRP3; NOD-like receptor; inflammasome; inflammatory diseases; inhibitors; innate immune system.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The NLRP3 inflammasome pathway and its inhibitors.
Figure 2
Figure 2
Sulfonamide-based NLRP3 inhibitors structures.
Figure 3
Figure 3
Natural product NLRP3 inhibitors structures.
Figure 4
Figure 4
Other NLRP3 inhibitors structures.
See this image and copyright information in PMC

References

    1. Agnew A., Nulty C., Creagh E. M. (2021). Regulation, activation and function of caspase-11 during health and disease. Int. J. Mol. Sci. 22:1506. 10.3390/ijms22041506 - DOI - PMC - PubMed
    1. Ahn H., Kang S. G., Yoon S. I., Ko H. J., Kim P. H., Hong E. J., et al. . (2017). Methylene blue inhibits NLRP3, NLRC4, AIM2 and non-canonical inflammasome activation. Sci. Rep. 7:12409. 10.1038/s41598-017-12635-6 - DOI - PMC - PubMed
    1. Allam R., Lawlor K. E., Yu E. C., Mildenhall A. L., Moujalled D. M., Lewis R. S., et al. . (2014). Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non-apoptotic caspase-8 is required for inflammasome priming. EMBO Rep. 15, 982–990. 10.15252/embr.201438463 - DOI - PMC - PubMed
    1. Alwaseem H., Frisch B. J., Fasan R. (2018). Anticancer activity profiling of parthenolide analogs generated via P450-mediated chemoenzymatic synthesis. Bioorg. Med. Chem. 26, 1365–1373. 10.1016/j.bmc.2017.08.009 - DOI - PMC - PubMed
    1. Amanzadeh E., Esmaeili A., Rahgozar S., Nourbakhshnia M. (2019). Application of quercetin in neurological disorders: from nutrition to nanomedicine. Rev. Neurosci. 30, 555–572. 10.1515/revneuro-2018-0080 - DOI - PubMed