Life span has almost doubled in the last century, and aging-specific diseases are now becoming prevalent. Every day, our cells are damaged by free radicals from natural processes of living cells which is inevitable but can be slowed down by body’s inherent antioxidant mechanism. The Nrf2 antioxidant response pathway plays an important role in cellular antioxidant defence. The case for Nrf2 is compelling. It is now widely recognized because of the versatile and comprehensive cytoprotective roles of the proteins encoded by NRF2-target genes, including antioxidant, detoxification and anti-inflammatory proteins. Nrf2 is known in scientific circles as the ‘master regulator’ because it also controls immune and inflammatory responses, tissue remodelling, cancer formation and cognitive dysfunction. Nrf2 activation causes inhibition of inflammation, improvement of mitochondrial function, and maintenance of protein homeostasis.
Studies have shown Nrf2 protective effects against cancer, asthma, organ degeneration, inflammation, autoimmune, respiratory, digestive, cardiovascular, metabolic, and neurodegenerative diseases, along with cancer and aging.
Currently, there are over 250 identical NRF2 target genes involved in a multitude of cellular processes, including redox regulation, drug metabolism, protein homeostasis, DNA repair, carbohydrate and lipid metabolism, iron homeostasis, transcriptional regulation and mitochondrial function. Nrf2 modulates for corrective measures of metabolic, inflammatory and autoimmune disorders; diseases of the lung, liver, kidney, gastrointestinal (GI) tract and cardiovascular system and neurological conditions.
Upon exposure to oxidative stress or other ARE activators, Nrf2 is released from Keap1 and gets translocated to the nucleus, where it can bind to the ARE, leading to the expression of antioxidant and phase II enzymes that protect the cell from oxidative damage. It regulates the expression of anti-oxidant proteins that protect the body against oxidative damage triggered by injury and inflammation. A hallmark of many chronic diseases is the loss of homeostatic responses such as redox signaling, metabolic flexibility, controlled inflammation and proteostasis. The multifactorial nature of these complex diseases could be targeted with one single hit at the transcription factor NRF2 as its activation elicits beneficial comprehensive, ‘multi-target’ and long-lasting cytoprotective effects.