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Inflammasomes as therapeutic targets in human diseases

Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals. Inflammasome multiprotein complexes are composed of three parts: a sensor protein, an adaptor, and pro-caspase-1. Activation of the infla...

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Autores principales: Li, Yangxin, Huang, Hui, Liu, Bin, Zhang, Yu, Pan, Xiangbin, Yu, Xi-Yong, Shen, Zhenya, Song, Yao-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249422/
https://www.ncbi.nlm.nih.gov/pubmed/34210954
http://dx.doi.org/10.1038/s41392-021-00650-z
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author Li, Yangxin
Huang, Hui
Liu, Bin
Zhang, Yu
Pan, Xiangbin
Yu, Xi-Yong
Shen, Zhenya
Song, Yao-Hua
author_facet Li, Yangxin
Huang, Hui
Liu, Bin
Zhang, Yu
Pan, Xiangbin
Yu, Xi-Yong
Shen, Zhenya
Song, Yao-Hua
author_sort Li, Yangxin
collection PubMed
description Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals. Inflammasome multiprotein complexes are composed of three parts: a sensor protein, an adaptor, and pro-caspase-1. Activation of the inflammasome leads to the activation of caspase-1, which cleaves pro-inflammatory cytokines such as IL-1β and IL-18, leading to pyroptosis. Effectors of the inflammasome not only provide protection against infectious pathogens, but also mediate control over sterile insults. Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases, cancer, and neurodegenerative disorders. Here, we review the role of the inflammasome as a double-edged sword in various diseases, and the outcomes can be either good or bad depending on the disease, as well as the genetic background. We highlight inflammasome memory and the two-shot activation process. We also propose the M- and N-type inflammation model, and discuss how the inflammasome pathway may be targeted for the development of novel therapy.
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spelling pubmed-82494222021-07-20 Inflammasomes as therapeutic targets in human diseases Li, Yangxin Huang, Hui Liu, Bin Zhang, Yu Pan, Xiangbin Yu, Xi-Yong Shen, Zhenya Song, Yao-Hua Signal Transduct Target Ther Review Article Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals. Inflammasome multiprotein complexes are composed of three parts: a sensor protein, an adaptor, and pro-caspase-1. Activation of the inflammasome leads to the activation of caspase-1, which cleaves pro-inflammatory cytokines such as IL-1β and IL-18, leading to pyroptosis. Effectors of the inflammasome not only provide protection against infectious pathogens, but also mediate control over sterile insults. Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases, cancer, and neurodegenerative disorders. Here, we review the role of the inflammasome as a double-edged sword in various diseases, and the outcomes can be either good or bad depending on the disease, as well as the genetic background. We highlight inflammasome memory and the two-shot activation process. We also propose the M- and N-type inflammation model, and discuss how the inflammasome pathway may be targeted for the development of novel therapy. Nature Publishing Group UK 2021-07-02 /pmc/articles/PMC8249422/ /pubmed/34210954 http://dx.doi.org/10.1038/s41392-021-00650-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Review Article
Li, Yangxin
Huang, Hui
Liu, Bin
Zhang, Yu
Pan, Xiangbin
Yu, Xi-Yong
Shen, Zhenya
Song, Yao-Hua
Inflammasomes as therapeutic targets in human diseases
title Inflammasomes as therapeutic targets in human diseases
title_full Inflammasomes as therapeutic targets in human diseases
title_fullStr Inflammasomes as therapeutic targets in human diseases
title_full_unstemmed Inflammasomes as therapeutic targets in human diseases
title_short Inflammasomes as therapeutic targets in human diseases
title_sort inflammasomes as therapeutic targets in human diseases
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249422/
https://www.ncbi.nlm.nih.gov/pubmed/34210954
http://dx.doi.org/10.1038/s41392-021-00650-z
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