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Gasdermins: New Therapeutic Targets in Host Defense, Inflammatory Diseases, and Cancer
Gasdermins (GSDMs) are a class of pore-forming proteins related to pyroptosis, a programmed cell death pathway that is induced by a range of inflammatory stimuli. Small-scale GSDM activation and pore formation allow the passive release of cytokines, such as IL-1β and IL-18, and alarmins, but, whenev...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285118/ https://www.ncbi.nlm.nih.gov/pubmed/35844522 http://dx.doi.org/10.3389/fimmu.2022.898298 |
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author | Magnani, Laura Colantuoni, Mariasilvia Mortellaro, Alessandra |
author_facet | Magnani, Laura Colantuoni, Mariasilvia Mortellaro, Alessandra |
author_sort | Magnani, Laura |
collection | PubMed |
description | Gasdermins (GSDMs) are a class of pore-forming proteins related to pyroptosis, a programmed cell death pathway that is induced by a range of inflammatory stimuli. Small-scale GSDM activation and pore formation allow the passive release of cytokines, such as IL-1β and IL-18, and alarmins, but, whenever numerous GSDM pores are assembled, osmotic lysis and cell death occur. Such GSDM-mediated pyroptosis promotes pathogen clearance and can help restore homeostasis, but recent studies have revealed that dysregulated pyroptosis is at the root of many inflammation-mediated disease conditions. Moreover, new homeostatic functions for gasdermins are beginning to be revealed. Here, we review the newly discovered mechanisms of GSDM activation and their prominent roles in host defense and human diseases associated with chronic inflammation. We also highlight the potential of targeting GSDMs as a new therapeutic approach to combat chronic inflammatory diseases and cancer and how we might overcome the current obstacles to realize this potential. |
format | Online Article Text |
id | pubmed-9285118 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92851182022-07-16 Gasdermins: New Therapeutic Targets in Host Defense, Inflammatory Diseases, and Cancer Magnani, Laura Colantuoni, Mariasilvia Mortellaro, Alessandra Front Immunol Immunology Gasdermins (GSDMs) are a class of pore-forming proteins related to pyroptosis, a programmed cell death pathway that is induced by a range of inflammatory stimuli. Small-scale GSDM activation and pore formation allow the passive release of cytokines, such as IL-1β and IL-18, and alarmins, but, whenever numerous GSDM pores are assembled, osmotic lysis and cell death occur. Such GSDM-mediated pyroptosis promotes pathogen clearance and can help restore homeostasis, but recent studies have revealed that dysregulated pyroptosis is at the root of many inflammation-mediated disease conditions. Moreover, new homeostatic functions for gasdermins are beginning to be revealed. Here, we review the newly discovered mechanisms of GSDM activation and their prominent roles in host defense and human diseases associated with chronic inflammation. We also highlight the potential of targeting GSDMs as a new therapeutic approach to combat chronic inflammatory diseases and cancer and how we might overcome the current obstacles to realize this potential. Frontiers Media S.A. 2022-07-01 /pmc/articles/PMC9285118/ /pubmed/35844522 http://dx.doi.org/10.3389/fimmu.2022.898298 Text en Copyright © 2022 Magnani, Colantuoni and Mortellaro https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Magnani, Laura Colantuoni, Mariasilvia Mortellaro, Alessandra Gasdermins: New Therapeutic Targets in Host Defense, Inflammatory Diseases, and Cancer |
title | Gasdermins: New Therapeutic Targets in Host Defense, Inflammatory Diseases, and Cancer |
title_full | Gasdermins: New Therapeutic Targets in Host Defense, Inflammatory Diseases, and Cancer |
title_fullStr | Gasdermins: New Therapeutic Targets in Host Defense, Inflammatory Diseases, and Cancer |
title_full_unstemmed | Gasdermins: New Therapeutic Targets in Host Defense, Inflammatory Diseases, and Cancer |
title_short | Gasdermins: New Therapeutic Targets in Host Defense, Inflammatory Diseases, and Cancer |
title_sort | gasdermins: new therapeutic targets in host defense, inflammatory diseases, and cancer |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285118/ https://www.ncbi.nlm.nih.gov/pubmed/35844522 http://dx.doi.org/10.3389/fimmu.2022.898298 |
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