INTERESTS: Stress response, Transcription, Inflammation.
Environmental stress response mechanism for healthy aging.
A process of organismal aging is greatly influenced by its environment. KEAP1-NRF2 system is one of our most important defense mechanisms from environmental stresses. NRF2 is a master transcriptional activator playing a critical role in the cytoprotection from oxidative and electrophilic insults. Under unstressed conditions, NRF2 is bound by KEAP1 and constantly ubiquitinated and degraded in proteasome. Upon exposure to oxidative stress or electrophilic toxicants, NRF2 is stabilized, activates transcription and confers resistance against the oxidative stress. Our recent studies have revealed that NRF2 has a potent anti-inflammatory activity in addition to the antioxidant activity. In particular, NRF2 activation significantly decreases expression of pro-inflammatory cytokine genes that are involved in the senescence-associated secretory phenotype (SASP), suggesting that NRF2 activation is effective for antagonizing SASP and prevent aging-related disorders. Our recent results in the analysis on effects of NRF2 activation in Alzheimer’s disease model mice will be presented.