The Crosstalk Between Nrf2 and Pyroptosis in Diseases Publisher Pubmed



Wang X ; Monemi M ; Moghadam F M ; Fazilat A ; Roshani S ; Valilo M
Source: Pathology, research and practice Published:2025

Abstract

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor involved in the regulation of various genes, including cell protection genes and genes encoding detoxification enzymes, metabolic enzymes, drug transporters, inflammation-related proteins, and antioxidant enzymes. Nrf2 itself is regulated by mechanisms induced by Kelch-like ECH-associated protein 1 (KEAP1) in response to electrophilic and oxidative stresses. One type of cell death is pyroptosis. In this type of cell death, the cell expands, the cell membrane ruptures, and the cell contents are released, which activates immune and inflammatory responses. The activation of these inflammatory pathways triggers caspase-1 or caspase-4/5/11, which can further cleave gasdermin D (GSDMD). The N-terminal region of GSDMD, upon release, binds to membrane lipids and disrupts the cell membrane. According to the literature, Nrf2 reduces the levels of reactive oxygen species (ROS) and suppresses pyroptosis. Therefore, based on this finding and considering the importance of pyroptosis in cell death and its relationship with Nrf2, this study aimed to explore the relationship between pyroptosis and Nrf2 in different diseases. Copyright © 2025. Published by Elsevier GmbH.