Using a new mouse model whose liver cells express a KEAP1-resistant form of NRF2, Karin and collaborators found that persistent activation of NRF2 in these mice resulted in rapid and dramatic enlargement of the liver, known as hepatomegaly. Some researchers now believe cancer cells may actually use NRF2 to protect themselves from radiation and chemotherapeutics. Many such compounds are being sold at health food stores as anti-aging remedies."īut research in recent years has found that several cancers, including liver and lung cancers, harbor mutations that decouple NRF2 from KEAP1, suggesting that persistent NRF2 activation may not be such a good thing after all.
![nrf2 activator nrf2 activator](https://www.frontiersin.org/files/Articles/561998/fpsyt-11-561998-HTML/image_m/fpsyt-11-561998-g001.jpg)
"And much effort has been dedicated to the development of NRF2 activators for cancer prevention and age-related diseases. "By being able to reduce the devastating impact of oxidative stress, the KEAP1-NRF2 system has long been thought to protect us from cancer and aging," said Karin.
#NRF2 ACTIVATOR CODE#
NRF2 levels subsequently build within the cell with the protein entering the nucleus, where it stimulates expression of numerous genes that code for enzymes and other proteins that detoxify harmful oxidants. When cells are healthy and unstressed by oxidants, levels of NRF2 are kept low by KEAP1 (Kelch-like ECH-associated protein 1), which is constantly degrading NRF2.īut in response to oxidative stress, KEAP1 is inactivated, releasing NRF2 from its inhibitory grip. NRF2 (Nuclear factor erythroid 2-related factor 2) is the master regulator of the antioxidant response.
![nrf2 activator nrf2 activator](https://europepmc.org/articles/PMC6223233/bin/fx1.jpg)
In a new study, published Februin the Journal of Hepatology, a team of scientists, led by postdoctoral fellows Feng He, PhD, and Laura Antonucci, PhD, and senior author Michael Karin, PhD, Distinguished Professor of Pharmacology and Pathology at University of California San Diego School of Medicine, suggest prolonged exposure to NRF2 and KEAP1 may contribute to enlargement of the liver and fatty liver diseases.