Abstract
Inflammatory diseases compromise a clinically common and diverse group of conditions, causing detrimental effects on body functions. Gasdermins (GSDM) are pore-forming proteins, playing pivotal roles in modulating inflammation. Belonging to the GSDM family, gasdermin D (GSDMD) actively mediates the pathogenesis of inflammatory diseases by mechanistically regulating different forms of cell death, particularly pyroptosis, and cytokine release, in an inflammasome-dependent manner. Aberrant activation of GSDMD in different types of cells, such as immune cells, cardiovascular cells, pancreatic cells and hepatocytes, critically contributes to the persistent inflammation in different tissues and organs. The contributory role of GSDMD has been implicated in diabetes mellitus, liver diseases, cardiovascular diseases, neurodegenerative diseases, and inflammatory bowel disease (IBD). Clinically, alterations in GSDMD levels are potentially indicative to the occurrence and severity of diseases. GSDMD inhibition might represent an attractive therapeutic direction to counteract the progression of inflammatory diseases, whereas a number of GSDMD inhibitors have been shown to restrain GSDMD-mediated pyroptosis through different mechanisms. This review discusses the current understanding and future perspectives on the role of GSDMD in the development of inflammatory diseases, as well as the clinical insights of GSDMD alterations, and therapeutic potential of GSDMD inhibitors against inflammatory diseases. Further investigation on the comprehensive role of GSDM shall deepen our understanding towards inflammation, opening up more diagnostic and therapeutic opportunities against inflammatory diseases. © 2024 Cheng, Yi, Wang and Huang
| Original language | English |
|---|---|
| Article number | 1456244 |
| Number of pages | 16 |
| Journal | Frontiers in Immunology |
| Volume | 15 |
| DOIs | |
| Publication status | Published - 26 Aug 2024 |
Funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by Hong Kong Research Grants Council (1103222, SRFS2021-4S04, T12-101/23-N, 14109720), and the City University of Hong Kong Start-up Fund. This work was also substantially supported by a fellowship award from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. CityU PDFS2223-1S01).
UN SDGs
This output contributes to the following UN Sustainable Development Goals (SDGs)
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SDG 3 Good Health and Well-being
Publisher's Copyright Statement
- This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/
RGC Funding Information
- RGC-funded
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