NRF2 is a basic leucine zipper (bZIP) protein that binds to antioxidant response elements (AREs) in the promoter regions of genes encoding cytoprotective proteins . This binding induces the expression of various genes involved in the cellular response to oxidative stress, including phase II detoxifying enzymes . NRF2 is known to inhibit the NLRP3 inflammasome, which is involved in the inflammatory response .
The structure of NRF2 includes seven highly conserved domains known as NRF2-ECH homology (Neh) domains . These domains are responsible for various functions:
NRF2 is involved in a complex regulatory network that affects metabolism, inflammation, autophagy, proteostasis, mitochondrial physiology, and immune responses . Due to its role in protecting cells from oxidative stress, NRF2 is a promising therapeutic target for diseases caused by oxidative damage, such as neurodegenerative diseases, cardiovascular diseases, and cancer .
Several drugs that stimulate the NFE2L2 pathway are currently being studied for their potential to treat these conditions . The ability of NRF2 to regulate the expression of cytoprotective genes makes it a valuable target for developing new therapeutic strategies.
In vitro studies have shown that NRF2 binds to AREs in the promoter regions of genes encoding cytoprotective proteins, leading to the upregulation of these genes . This has significant implications for developing treatments that can enhance the body’s natural defense mechanisms against oxidative stress.
Human recombinant NRF2 is used in research to study its effects on gene expression and its potential therapeutic applications. By understanding how NRF2 functions and regulates gene expression, researchers can develop new strategies to combat diseases associated with oxidative stress.