The activation ofNRF2by KRAS-G12C inhibitors represents a unique example of anti-cancer drugs which positively regulate the activity of a protein which is normally considered to be an oncogene.
Arecent study demonstrated that T cell-specific activation ofNRF2increases the number of Tregs (), which suggests thatNRF2inhibits the inflammatory response by potentiating Treg-mediated immune suppression. However, it remains unknown whetherNRF2has any inhibitory effects on autoimmune-mediated inflammation in a Treg-independent manner.
Nuclear factor erythroid 2-related factor 2 (NRF2) serves as a master transcriptional regulator of cellular antioxidant responses through orchestration of cytoprotective gene expression, establishing its significance as a therapeutic target in cerebral pathophysiology. Classical electrophilicNRF2activators, despite potent activation potential, exhibit paradoxically reduced therapeutic ...
This particular example perfectly highlights why A Systemic Nrf2 Activator is so captivating.
Finally, a systematic review and preclinical meta-analysis demonstrated the protective role ofNrf2in periodontitis, confirming thatNrf2activation inhibits oxidative stress and inflammation, thereby preventing disease progression [7].
Nrf2signaling is upregulated in various cancers, and there is a concern that prolonged activation ofNrf2could increase the risk for cancer [8]. However, many of the electrophilicNrf2activatorshave anti-cancer activity through their modification of other proteins.
Here, we show thatNRF2maintains iron homeostasis by controlling HERC2 (E3 ubiquitin ligase for NCOA4 and FBXL5) and VAMP8 (mediates autophagosome-lysosome fusion). NFE2L2/NRF2knockout cells have low HERC2 expression, leading to a simultaneous increase in ferritin and NCOA4 and recruitment of apoferritin into the autophagosome.
