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Pyroptosis: Induction and inhibition strategies for immunotherapy of diseases
Junjun Wu1, Hong Wang1, Pu Gao2
1Key Laboratory of Microbial Pathogenesis and Interventions of Fujian Province University, the Key Laboratory of Innate Immune Biology of Fujian Province, Biomedical Research Center of South China, Key Laboratory of OptoElectronic Science and Technology for Medicine of the Ministry of Education, College of Life Sciences, Fujian Normal University, Fuzhou 350117, China.
Abstract:
Cell death is a central process for organismal health. Pyroptosis, namely pyroptotic cell death, is recognized as a critical type that disrupts membrane and triggers pro-inflammatory cytokine secretion via gasdermins, providing a robust form of cytolysis. Meanwhile, along with the thorough research, a great deal of evidence has demonstrated the dual effects of pyroptosis in host defense and inflammatory diseases. More importantly, the recent identification of abundant gasdermin-like proteins in bacteria and fungi suggests an ancient origin of pyroptosis-based regulated cell death in the life evolution. In this review, we bring a general overview of pyroptosis pathways focusing on gasdermin structural biology, regulatory mechanisms, and recent progress in induction and inhibition strategies for disease treatment. We look forward to providing an insightful perspective for readers to comprehend the frame and challenges of the pyroptosis field, and to accelerating its clinical application.
Insights
Pyroptosis is a cell death form that disrupts cell membranes via gasdermins, impacting host defense and disease. Understanding pyroptosis mechanisms is key for developing new treatments.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Pyroptosis is a critical regulated cell death pathway involving gasdermin proteins.
- It plays a dual role in host defense and inflammatory diseases.
- Gasdermin-like proteins suggest an ancient evolutionary origin for pyroptosis.
Purpose of the Study:
- To provide an overview of pyroptosis pathways.
- To focus on gasdermin structural biology and regulatory mechanisms.
- To discuss recent advances in pyroptosis induction and inhibition for disease treatment.
Main Methods:
- Literature review of pyroptosis research.
- Analysis of gasdermin structure and function.
- Synthesis of current therapeutic strategies.
Main Results:
- Pyroptosis involves membrane disruption and pro-inflammatory cytokine release.
- Gasdermin proteins are central effectors of pyroptosis.
- Pyroptosis has implications in both beneficial host defense and detrimental inflammatory conditions.
Conclusions:
- Pyroptosis is an evolutionarily conserved cell death mechanism.
- Targeting pyroptosis offers potential therapeutic avenues for various diseases.
- Further research is needed to fully harness pyroptosis for clinical applications.
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