Basic Leucine Zipper Protein Nuclear Factor Erythroid 2–related Factor 2 as a Potential Therapeutic Target in Brain Related Disorders

Abstract

Abstract: Nuclear factor erythroid-2-related factor 2 (Nrf2), an inducible transcription factor in phase II metabolic reactions, as well as xenobiotic response pathway, is referred to as ‘master regulator’ in anti-oxidant, anti-inflammatory, and xenobiotic detoxification processes. The activity of Nrf2 is tightly regulated by KEAP1, which promotes ubiquitination, followed by degradation under homeostatic conditions and also allows Nrf2 to escape ubiquitination, accumulate within the cell, and translocate in the nucleus upon exposure to the stresses. The Nrf2 pathway has shown an intrinsic mechanism of defense against oxidative stress (OS). It emerged as a promising therapeutic target as both inducers and as there is an increasing number of evidence for the protective role of the Nrf2-ARE pathway towards exacerbations of ROS generation as well as OS, mitochondrial dysfunction as well as prolonged neuroinflammation is a prevalent pathophysiological process rooted in brain-related disorders. Elevated concentrations of ROS generation and OS have been linked to the pathophysiology of a diverse array of brain related disorders, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Friedrich’s ataxia, multiple sclerosis, and epilepsy. Further, it not only modulates the articulation of anti-oxidant genes but has often been associated with implicating anti-inflammatory consequences as well as regulating mitochondrial functionalities and biogenesis. Therefore, Nrf2 can be considered a potential therapeutic target for the regimen of various brain-related disorders.