ArticleProceedings of the National Academy of Sciences of the United States of America2022
The Gasdermin D N-terminal fragment acts as a negative feedback system to inhibit inflammasome-mediated activation of Caspase-1/11.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 44 citations in OpenAlex.
- The gasdermin family: from pyroptosis mechanisms to therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Exercise promotes host anti-infection activity through CNDP2 metabolite-mediated inflammasome hyperactivation.PLoS pathogens · 2026Article
- A peripheral subpopulation of retinal pigment epithelium resists oxidative damage through SERPINE3-mediated caspase-1 inhibition.The Journal of clinical investigation · 2026Article
- Gasdermin D in Neurodegenerative Diseases: Pathogenic Roles and Therapeutic Perspectives.Molecular neurobiology · 2026Review
- Angiotensin-(1-7) suppresses pyroptosis in cerebral endothelium to decrease blood-brain barrier permeability and cognitive impairments in sepsis.The Journal of international medical research · 2026Article
- Regulation of inflammatory processes by caspases.Nature reviews. Molecular cell biology · 2025Review
- M464 inhibits activation of NLRP3 inflammasome and inflammatory response in mice.Scientific reports · 2025Article
- The Neglected Role of GSDMD C-Terminal in Counteracting Type I Interferon Signaling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting inflammasomes as an immunotherapeutic strategy for cancer.Journal of translational medicine · 2025Review
- Emodin influences pyroptosis-related Caspase 1-GSDMD axis alleviated cerebral ischemia-reperfusion injury in rats.Scientific reports · 2025Article
- Exploring the role of palmitoylation in sepsis: mechanistic insights and future perspectives.Molecular medicine (Cambridge, Mass.) · 2025Review
- miR-126-5p protects from URSA via inhibiting Caspase-1-dependent pyroptosis of trophoblast cells.Cellular and molecular life sciences : CMLS · 2025Article
- Gasdermin-D Genetic Knockout Reduces Inflammasome-Induced Disruption of the Gut-Brain Axis After Traumatic Brain Injury.International journal of molecular sciences · 2025Article
- Nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 inflammasome: From action mechanism to therapeutic target in clinical trials.World journal of gastrointestinal oncology · 2025Article
- Therapeutic strategies of targeting non-apoptotic regulated cell death (RCD) with small-molecule compounds in cancer.Acta pharmaceutica Sinica. B · 2024Review
- Article
- Bucket lists must be completed during cell death.Trends in cell biology · 2023Review
- Molecular mechanisms of gasdermin D pore-forming activity.Nature immunology · 2023Review
- Article
- Hepatocyte-specific regulation of autophagy and inflammasome activation via MyD88 during lethalFrontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammatory pathways usually utilize negative feedback regulatory systems to prevent tissue damage arising from excessive inflammatory response. Whether such negative feedback mechanisms exist in inflammasome activation remains unknown. Gasdermin D (GSDMD) is the pyroptosis executioner of downstream inflammasome signaling. Here, we found that GSDMD, after its cleavage by caspase-1/11, utilizes its RFWK motif in the N-terminal β1-β2 loop to inhibit the activation of caspase-1/11 and downstream inflammation in a negative feedback manner. Furthermore, an RFWK motif-based peptide inhibitor can inhibit caspase-1/11 activation and its downstream substrates GSDMD and interleukin-1β cleavage, as well as lipopolysaccharide-induced sepsis in mice. Collectively, these findings provide a demonstration of the N-terminal fragment of GSDMD as a negative feedback regulator controlling inflammasome activation and a detailed delineation of the underlying inhibitory mechanism.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.