Article of Significant Interest in This Issue

Nrf2 Plays Critical Roles in Controlling Stresses in Alzheimer’s Disease Mouse Brain

The oxidative stress response in the brain is critically relevant to the pathogenesis of Alzheimer’s disease (AD). It is therefore important to understand how it is regulated. Transcription factor Nrf2 regulates antioxidant gene expression and protects cells against stresses. Uruno et al. (e00467-19) demonstrate that Nrf2 induction upregulates the expression of anti-oxidative stress genes and downregulates the expression of proinflammatory cytokine genes in brain in a mouse model of AD. Nrf2 is also shown to increase glutathione levels and to repress microglia activation. Most importantly, Nrf2 suppression of oxidative stress and inflammation is found to elicit improvement of cognitive impairment in AD model mice. These findings identify Nrf2 as a potential therapeutic target for the treatment of AD.