Small molecule modulators of antioxidant response pathway.

Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that regulates Antioxidant Response Element (ARE)-mediated transcription of a plethora of antioxidant and protective genes to counteract the harmful effects of reactive oxygen species or environmental carcinogens. Studies have demonstrated that pre-emptive activation of the Nrf2-ARE pathway reinforces the cellular defense mechanism against oxidative stress and leads to protection in a variety of disease models. Non-carcinogenic ARE inducers have been identified from a variety of chemical classes that enhance the transcriptional activity of Nrf2 through S-alkylation of reactive cysteines within the cellular redox sensor protein Keap1 (Kelch-like ECH associated protein 1). Here we review the currently known small molecule ARE inducers and their reported biological activities in various models.