KEAP1 and neurodegenerative disease: Nrf2 has emerged as the main cellular defense mechanism against many harmful environmental toxicants, carcinogens and inducers of neurodegenerative diseases including genetic accelerated age-related hearing loss [48, 83, 84]. Under normal redox conditions, Nrf2 is inactive due to its cytoplasmic retention by Keap1 (Kelch-like ECH-associated protein 1) and rapid degradation by the proteasome system [83].