NRF2 PATHWAY INVOLVEMENT IN THE CENTRAL NERVOUS SYSTEM

The nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway plays a fundamental role in cellular defense
against oxidative and electrophilic stress. Within the central nervous system (CNS), where neurons and glial cells
are highly susceptible to oxidative damage, Nrf2 has emerged as a master regulator of antioxidant and detoxification
responses. Activation of Nrf2 upregulates a wide array of genes involved in maintaining redox balance, including
heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and enzymes responsible for glutathione
synthesis. These adaptive responses help protect neurons from oxidative injury and support overall brain
homeostasis. Dysregulation of Nrf2 signaling is increasingly recognized as a critical factor in the pathogenesis of
neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic
lateral sclerosis, and multiple sclerosis, as well as in acute neurological injuries like ischemic stroke and traumatic
brain injury. Pharmacological strategies to activate Nrf2, including synthetic compounds such as dimethyl fumarate
and natural agents like sulforaphane, have shown promising neuroprotective effects in both experimental and
clinical settings. This review provides a comprehensive discussion on the structure and regulation of the Nrf2
pathway, its physiological role in the CNS, its involvement in neurological diseases, and therapeutic approaches
targeting Nrf2 signaling.