NLRP Inflammasomes in Health and Disease

Overview

Journal Mol Biomed

Specialties Biomedical Engineering
General Medicine
Pathology

Date 2024 Apr 21

PMID 38644450

Authors

Zhihao Xu

Arnaud John Kombe Kombe

Shasha Deng

Hongliang Zhang

Songquan Wu

Jianbin Ruan

Ying Zhou

Tengchuan Jin

Affiliations

Soon will be listed here.

Abstract

NLRP inflammasomes are a group of cytosolic multiprotein oligomer pattern recognition receptors (PRRs) involved in the recognition of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) produced by infected cells. They regulate innate immunity by triggering a protective inflammatory response. However, despite their protective role, aberrant NLPR inflammasome activation and gain-of-function mutations in NLRP sensor proteins are involved in occurrence and enhancement of non-communicating autoimmune, auto-inflammatory, and neurodegenerative diseases. In the last few years, significant advances have been achieved in the understanding of the NLRP inflammasome physiological functions and their molecular mechanisms of activation, as well as therapeutics that target NLRP inflammasome activity in inflammatory diseases. Here, we provide the latest research progress on NLRP inflammasomes, including NLRP1, CARD8, NLRP3, NLRP6, NLRP7, NLRP2, NLRP9, NLRP10, and NLRP12 regarding their structural and assembling features, signaling transduction and molecular activation mechanisms. Importantly, we highlight the mechanisms associated with NLRP inflammasome dysregulation involved in numerous human auto-inflammatory, autoimmune, and neurodegenerative diseases. Overall, we summarize the latest discoveries in NLRP biology, their forming inflammasomes, and their role in health and diseases, and provide therapeutic strategies and perspectives for future studies about NLRP inflammasomes.

Citing Articles

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References

Taabazuing C, Okondo M, Bachovchin D . Pyroptosis and Apoptosis Pathways Engage in Bidirectional Crosstalk in Monocytes and Macrophages. Cell Chem Biol. 2017; 24(4):507-514.e4. PMC: 5467448. DOI: 10.1016/j.chembiol.2017.03.009. View

Xu X, Zhu X, Wang C, Li Y, Fan C, Kao X . microRNA-650 promotes inflammation induced apoptosis of intestinal epithelioid cells by targeting NLRP6. Biochem Biophys Res Commun. 2019; 517(4):551-556. DOI: 10.1016/j.bbrc.2019.06.077. View

Okondo M, Rao S, Taabazuing C, Chui A, Poplawski S, Johnson D . Inhibition of Dpp8/9 Activates the Nlrp1b Inflammasome. Cell Chem Biol. 2018; 25(3):262-267.e5. PMC: 5856610. DOI: 10.1016/j.chembiol.2017.12.013. View

Jin T, Curry J, Smith P, Jiang J, Xiao T . Structure of the NLRP1 caspase recruitment domain suggests potential mechanisms for its association with procaspase-1. Proteins. 2013; 81(7):1266-70. PMC: 3860829. DOI: 10.1002/prot.24287. View

Ozretic P, da Silva Filho M, Catalano C, Sokolovic I, Vukic-Dugac A, Sutic M . Association of Coding Polymorphism with Lung Function and Serum IL-1β Concentration in Patients Diagnosed with Chronic Obstructive Pulmonary Disease (COPD). Genes (Basel). 2019; 10(10). PMC: 6826440. DOI: 10.3390/genes10100783. View

Yanling Q, Xiaoning C, Fei B, Liyun F, Huizhong H, Daqing S . Inhibition of NLRP9b attenuates acute lung injury through suppressing inflammation, apoptosis and oxidative stress in murine and cell models. Biochem Biophys Res Commun. 2018; 503(2):436-443. DOI: 10.1016/j.bbrc.2018.04.079. View

Uchiyama A, Kosaka K, Okada K, Motegi S . Possible suppressive effects of tranilast on NLRP3 inflammasome activation in necrobiosis lipoidica. J Dermatol. 2022; 49(12):e433-e434. DOI: 10.1111/1346-8138.16521. View

Braga T, Forni M, Correa-Costa M, Ramos R, Barbuto J, Branco P . Soluble Uric Acid Activates the NLRP3 Inflammasome. Sci Rep. 2017; 7:39884. PMC: 5233987. DOI: 10.1038/srep39884. View

Dempsey C, Rubio Araiz A, Bryson K, Finucane O, Larkin C, Mills E . Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-β and cognitive function in APP/PS1 mice. Brain Behav Immun. 2016; 61:306-316. DOI: 10.1016/j.bbi.2016.12.014. View

10.

Johnson D, Taabazuing C, Okondo M, Chui A, Rao S, Brown F . DPP8/DPP9 inhibitor-induced pyroptosis for treatment of acute myeloid leukemia. Nat Med. 2018; 24(8):1151-1156. PMC: 6082709. DOI: 10.1038/s41591-018-0082-y. View

11.

Zheng D, Mohapatra G, Kern L, He Y, Shmueli M, Valdes-Mas R . Epithelial Nlrp10 inflammasome mediates protection against intestinal autoinflammation. Nat Immunol. 2023; 24(4):585-594. DOI: 10.1038/s41590-023-01450-z. View

12.

Amoushahi M, Steffensen L, Galieva A, Agger J, Heuck A, Siupka P . Maternally contributed Nlrp9b expressed in human and mouse ovarian follicles contributes to early murine preimplantation development. J Assist Reprod Genet. 2020; 37(6):1355-1365. PMC: 7311623. DOI: 10.1007/s10815-020-01767-w. View

13.

Wu X, Li K, Yang H, Yang B, Lu X, Zhao L . Complement C1q synergizes with PTX3 in promoting NLRP3 inflammasome over-activation and pyroptosis in rheumatoid arthritis. J Autoimmun. 2019; 106:102336. DOI: 10.1016/j.jaut.2019.102336. View

14.

Jayabalan N, Oronsky B, Cabrales P, Reid T, Caroen S, Johnson A . A Review of RRx-001: A Late-Stage Multi-Indication Inhibitor of NLRP3 Activation and Chronic Inflammation. Drugs. 2023; 83(5):389-402. PMC: 10015535. DOI: 10.1007/s40265-023-01838-z. View

15.

Codolo G, Plotegher N, Pozzobon T, Brucale M, Tessari I, Bubacco L . Triggering of inflammasome by aggregated α-synuclein, an inflammatory response in synucleinopathies. PLoS One. 2013; 8(1):e55375. PMC: 3561263. DOI: 10.1371/journal.pone.0055375. View

16.

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

17.

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

18.

Wang Q, Hsiao J, Yardeny N, Huang H, OMara C, Orth-He E . The NLRP1 and CARD8 inflammasomes detect reductive stress. Cell Rep. 2023; 42(1):111966. PMC: 9942139. DOI: 10.1016/j.celrep.2022.111966. View

19.

Guan K, Wei C, Zheng Z, Song T, Wu F, Zhang Y . MAVS Promotes Inflammasome Activation by Targeting ASC for K63-Linked Ubiquitination via the E3 Ligase TRAF3. J Immunol. 2015; 194(10):4880-90. DOI: 10.4049/jimmunol.1402851. View

20.

Radian A, de Almeida L, Dorfleutner A, Stehlik C . NLRP7 and related inflammasome activating pattern recognition receptors and their function in host defense and disease. Microbes Infect. 2013; 15(8-9):630-9. PMC: 3722249. DOI: 10.1016/j.micinf.2013.04.001. View