An update on the role of Nrf2 and its activators in diseases associated with oxidative stress

Abstract

A wide range of experimental and observational studies have established the irrefutable role of oxidative stress in the pathogenesis of a plethora of diseases either directly or indirectly. Several factors ranging from radiation, pollution, high fat and sugar diet, alcohol consumption, smoking, tobacco consumption and even certain drugs contribute to oxidative stress. The imbalance between oxidant and antioxidant levels remain the underlying cause of oxidative stress. When the levels of oxidants outweigh the levels of antioxidants it leads to formation of free radicals like hydroxyl, superoxide, alkoxyl, peroxyl, glutathiyl, tocopheroxyl, hydroperoxyl and ascorbate. These free radical species play a definitive role in the pathogenesis of neurological diseases, malignancies, cardiovascular, respiratory and liver diseases. Nuclear factor erythroid-2-related factor 2 is a master transcription factor belonging to the leucine zipper family. Kelch-like ECH-associated protein 1 is a repressor of nuclear factor erythroid-2-related factor 2 under basal or normal conditions, which is responsible for cytoplasmic sequestration and proteosomal degradation of nuclear factor erythroid-2-related factor 2 via ubiquitination. The activation of nuclear factor erythroid-2-related factor 2/Kelch-like ECH-associated protein 1/antioxidant response element signalling pathway regulates the expression of numbers of genes that are cytoprotective, antioxidative and detoxificative in action. This article reviews the potential therapeutic role of nuclear factor erythroid-2-related factor 2 activators in prevention and treatment of those diseases in which oxidative stress plays a definitive role in the pathogenesis.