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Pyroptosis Modulators: New Insights of Gasdermins in Health and Disease
Imane Allali-Boumara1, Ana Dácil Marrero1,2,3, Ana R Quesada1,2,3
1Andalucía Tech, Departamento de Biología Molecular y Bioquímica, Facultad de Ciencias, Universidad de Málaga, E-29071 Málaga, Spain.
Abstract:
Pyroptosis is an inflammation-dependent type of cell death that has been in the spotlight for the scientific community in the last few years. Crucial players in the process of pyroptosis are the members of the gasdermin family of proteins, which have been parallelly studied. Upon induction of pyroptosis, gasdermins suffer from structural changes leading to the formation of pores in the membrane that subsequently cause the release of pro-inflammatory contents. Recently, it has been discovered that oxidation plays a key role in the activation of certain gasdermins. Here, we review the current knowledge on pyroptosis and human gasdermins, focusing on the description of the different members of the family, their molecular structures, and their influence on health and disease directly or non-directly related to inflammation. Noteworthy, we have focused on the existing understanding of the role of this family of proteins in cancer, which could translate into novel promising strategies aimed at benefiting human health. In conclusion, the modulation of pyroptosis and gasdermins by natural and synthetic compounds through different mechanisms, including modification of the redox state of cells, has been proven effective and sets precedents for future therapeutic strategies.
Insights
Pyroptosis, an inflammatory cell death, involves gasdermin proteins forming pores. Oxidation influences gasdermin activation, offering new therapeutic strategies for inflammation and cancer.
Area of Science:
- Cellular Biology
- Immunology
- Biochemistry
Background:
- Pyroptosis is a key inflammatory cell death pathway.
- Gasdermin proteins are central effectors of pyroptosis, forming membrane pores.
- Oxidation is a newly identified regulator of gasdermin activation.
Purpose of the Study:
- To review current knowledge on pyroptosis and human gasdermins.
- To focus on gasdermin structure, function, and roles in health and disease.
- To highlight the role of gasdermins in cancer and potential therapeutic strategies.
Main Methods:
- Literature review of pyroptosis and gasdermin research.
- Analysis of molecular structures and functions of gasdermin family members.
- Synthesis of findings on gasdermins in inflammatory diseases and cancer.
Main Results:
- Gasdermins undergo structural changes to form pores, releasing inflammatory molecules.
- Oxidative modifications are critical for the activation of specific gasdermins.
- Gasdermin dysregulation is implicated in various inflammatory conditions and cancer progression.
Conclusions:
- Modulating pyroptosis and gasdermin activity, including via redox state, shows therapeutic promise.
- Targeting gasdermins offers novel strategies for treating inflammatory diseases and cancer.
- Further research into gasdermin-targeted therapies is warranted for human health benefits.
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