NLRP3 Inflammasome in Health and Disease (Review)

Overview

Journal Int J Mol Med

Specialty Genetics

Date 2025 Feb 11

PMID 39930811

Authors

Haoran Wang

Li Ma

Weiran Su

Yangruoyu Liu

Ning Xie

Jun Liu

Affiliations

Soon will be listed here.

Abstract

Activation of inflammasomes is the activation of inflammation‑related caspase mediated by the assembly signal of multi‑protein complex and the maturity of inflammatory factors, such as IL‑1β and IL‑18. Among them, the Nod‑like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most thoroughly studied type of inflammatory corpuscle at present, which is involved in the occurrence and development of numerous human diseases. Therefore, targeting the NLRP3 inflammasome has become the focus of drug development for related diseases. In this paper, the research progress of the NLRP3 inflammasome in recent years is summarized, including the activation and regulation of NLRP3 and its association with diseases. A deep understanding of the regulatory mechanism of NLRP3 will be helpful to the discovery of new drug targets and the development of therapeutic drugs.

References

Satoh M, Tabuchi T, Itoh T, Nakamura M . NLRP3 inflammasome activation in coronary artery disease: results from prospective and randomized study of treatment with atorvastatin or rosuvastatin. Clin Sci (Lond). 2013; 126(3):233-41. DOI: 10.1042/CS20130043. View

Chen F, Jiang G, Liu H, Li Z, Pei Y, Wang H . Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1β/NF-κB-NLRP3 inflammasome positive feedback loop. Bone Res. 2020; 8:10. PMC: 7028926. DOI: 10.1038/s41413-020-0087-2. View

Sandanger O, Ranheim T, Vinge L, Bliksoen M, Alfsnes K, Finsen A . The NLRP3 inflammasome is up-regulated in cardiac fibroblasts and mediates myocardial ischaemia-reperfusion injury. Cardiovasc Res. 2013; 99(1):164-74. DOI: 10.1093/cvr/cvt091. View

Zhou Y, Lu M, Du R, Qiao C, Jiang C, Zhang K . MicroRNA-7 targets Nod-like receptor protein 3 inflammasome to modulate neuroinflammation in the pathogenesis of Parkinson's disease. Mol Neurodegener. 2016; 11:28. PMC: 4833896. DOI: 10.1186/s13024-016-0094-3. View

Nakae S, Komiyama Y, Yokoyama H, Nambu A, Umeda M, Iwase M . IL-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response. Int Immunol. 2003; 15(4):483-90. DOI: 10.1093/intimm/dxg054. View

Wang L, Hauenstein A . The NLRP3 inflammasome: Mechanism of action, role in disease and therapies. Mol Aspects Med. 2020; 76:100889. DOI: 10.1016/j.mam.2020.100889. View

Lee H, Yang G, Kim N, Jeong S, Jung Y, Choi J . Targeting ASC in NLRP3 inflammasome by caffeic acid phenethyl ester: a novel strategy to treat acute gout. Sci Rep. 2016; 6:38622. PMC: 5146947. DOI: 10.1038/srep38622. View

Lima Jr H, Jacobson L, Goldberg M, Chandran K, Diaz-Griffero F, Lisanti M . Role of lysosome rupture in controlling Nlrp3 signaling and necrotic cell death. Cell Cycle. 2013; 12(12):1868-78. PMC: 3735701. DOI: 10.4161/cc.24903. View

Liu W, Guo W, Wu J, Luo Q, Tao F, Gu Y . A novel benzo[d]imidazole derivate prevents the development of dextran sulfate sodium-induced murine experimental colitis via inhibition of NLRP3 inflammasome. Biochem Pharmacol. 2013; 85(10):1504-12. DOI: 10.1016/j.bcp.2013.03.008. View

10.

Siegmund B, Fantuzzi G, Rieder F, Gamboni-Robertson F, Lehr H, Hartmann G . Neutralization of interleukin-18 reduces severity in murine colitis and intestinal IFN-gamma and TNF-alpha production. Am J Physiol Regul Integr Comp Physiol. 2001; 281(4):R1264-73. DOI: 10.1152/ajpregu.2001.281.4.R1264. View

11.

Zhang Y, Dong Z, Song W . NLRP3 inflammasome as a novel therapeutic target for Alzheimer's disease. Signal Transduct Target Ther. 2020; 5(1):37. PMC: 7109024. DOI: 10.1038/s41392-020-0145-7. View

12.

Idzko M, Hammad H, van Nimwegen M, Kool M, Willart M, Muskens F . Extracellular ATP triggers and maintains asthmatic airway inflammation by activating dendritic cells. Nat Med. 2007; 13(8):913-9. DOI: 10.1038/nm1617. View

13.

Muller T, Vieira R, Grimm M, Durk T, Cicko S, Zeiser R . A potential role for P2X7R in allergic airway inflammation in mice and humans. Am J Respir Cell Mol Biol. 2010; 44(4):456-64. DOI: 10.1165/rcmb.2010-0129OC. View

14.

Hornung V, Bauernfeind F, Halle A, Samstad E, Kono H, Rock K . Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 2008; 9(8):847-56. PMC: 2834784. DOI: 10.1038/ni.1631. View

15.

Zhou T, Xiang D, Li S, Yang L, Gao L, Feng C . MicroRNA-495 Ameliorates Cardiac Microvascular Endothelial Cell Injury and Inflammatory Reaction by Suppressing the NLRP3 Inflammasome Signaling Pathway. Cell Physiol Biochem. 2018; 49(2):798-815. DOI: 10.1159/000493042. View

16.

Dobson R, Giovannoni G . Multiple sclerosis - a review. Eur J Neurol. 2018; 26(1):27-40. DOI: 10.1111/ene.13819. View

17.

Dehlin M, Jacobsson L, Roddy E . Global epidemiology of gout: prevalence, incidence, treatment patterns and risk factors. Nat Rev Rheumatol. 2020; 16(7):380-390. DOI: 10.1038/s41584-020-0441-1. View

18.

Rosengren S, Hoffman H, Bugbee W, Boyle D . Expression and regulation of cryopyrin and related proteins in rheumatoid arthritis synovium. Ann Rheum Dis. 2004; 64(5):708-14. PMC: 1755498. DOI: 10.1136/ard.2004.025577. View

19.

Feldmeyer L, Keller M, Niklaus G, Hohl D, Werner S, Beer H . The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes. Curr Biol. 2007; 17(13):1140-5. DOI: 10.1016/j.cub.2007.05.074. View

20.

Wallisch J, Simon D, Bayir H, Bell M, Kochanek P, Clark R . Cerebrospinal Fluid NLRP3 is Increased After Severe Traumatic Brain Injury in Infants and Children. Neurocrit Care. 2017; 27(1):44-50. PMC: 5680164. DOI: 10.1007/s12028-017-0378-7. View