Abstract
Cellular defense mechanisms, intracellular signaling, and physiological functions are regulated by electrophiles and reactive oxygen species (ROS). Recent works strongly considered imbalanced ROS and electrophile overabundance as the leading cause of cellular and tissue damage, whereas oxidative stress (OS) plays a crucial role for the onset and progression of major cerebrovascular and neurodegenerative pathologies. These include Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Huntington’s disease (HD), stroke, and aging. Nuclear factor erythroid 2-related factor (NRF2) is the major modulator of the xenobiotic-activated receptor (XAR) and is accountable for activating the antioxidative response elements (ARE)-pathway modulating the detoxification and antioxidative responses of the cells. NRF2 activity, however, is also implicated in carcinogenesis protection, stem cells regulation, anti-inflammation, anti-aging, and so forth. Herein, we briefly describe the NRF2–ARE pathway and provide a review analysis of its functioning and system integration as well as its role in major CNS disorders. We also discuss NRF2-based therapeutic approaches for the treatment of neurodegenerative and cerebrovascular disorders.
Highlights
Oxidative stress (OS), one of the main indications of various pathologic processes, results from the production of reactive oxygen species (ROS) including hydrogen peroxide, superoxide, and hydroxyl free radicals
Cellular OS initiates a sequence of biological responses so that Nuclear factor erythroid 2-related factor (NRF2) translocates into the nucleus [17] where it forms a heterodimer with small Maf proteins (MafG, MafK, MafF)
We provide a detailed analysis of the current understanding of the NRF2–antioxidative response elements (ARE) system and its role in major CNS disorders
Summary
Oxidative stress (OS), one of the main indications of various pathologic processes, results from the production of ROS including hydrogen peroxide, superoxide, and hydroxyl free radicals. These highly reactive compounds promote lipid peroxidation, protein backbone fragmentation, genotoxicity, mitochondrial depolarization, and apoptosis that subsequently cause serious damage to tissues and organs including the brain [1,2,3]. The majority of this excessive reactive oxidative species is expected to be produced by oxidative phosphorylation responses in the mitochondria [4,5]. We include NRF2-focused therapeutic approaches for the treatment of cerebrovascular and neurodegenerative diseases
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