Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Our body possesses the ability to sense environmental stresses and activate cellular defense response. We have identified the KEAP1-NRF2 system. NRF2 is the transcription factor that plays a crucial role in the coordinated expression of cellular defense enzymes against oxidative and electrophilic stresses. KEAP1 acts as a sensor for these stresses and as a subunit of ubiquitin-E3 ligase that constantly degrades NRF2. Nrf2 gene knockout animals are sensitive to a broad array of toxic electrophiles and reactive oxygen species. In contrast, Keap1 gene knock-down animals exhibit a gain-of-function phenotype of NRF2. Modifications to the cysteine residues in KEAP1 negate its ubiquitin ligase activity, which stabilizes NRF2. Genetic as well as pharmacological inductions of NRF2 protect our body from the oxidative injury. We have demonstrated this activity in various disease models. The field continuously evolves with new topics emerging, including inflammation, metabolism, ageing, and neuroprotection by NRF2. Studies of the KEAP1-NRF2 system is now expanding toward human biology utilizing the cohort study of the Tohoku Medical Megabank and space mouse biology utilizing the International Space Station. Both historical contexts and recent advancements in the KEAP1-NRF2 system will be discussed.
