Overview of Nrf2 as Therapeutic Target in Epilepsy

Abstract

Oxidative stress is a biochemical state of imbalance in the production of reactive oxygen and nitrogen species and antioxidant defenses. It is involved in the physiopathology of degenerative and chronic neuronal disorders, such as epilepsy. Experimental evidence in humans and animals support the involvement of oxidative stress before and after seizures. In the past few years, research has increasingly focused on the molecular pathways of this process, such as that involving transcription factor nuclear factor E2-related factor 2 (Nrf2), which plays a central role in the regulation of antioxidant response elements (ARE) and modulates cellular redox status. The aim of this review is to present experimental evidence on the role of Nrf2 in this neurological disorder and to further determine the therapeutic impact of Nrf2 in epilepsy.

Alleviation of Oxidative Damage and Involvement of Nrf2‐ARE Pathway in Mesodopaminergic System and Hippocampus of Status Epilepticus Rats Pretreated by Intranasal Pentoxifylline

“…Nrf2 is a transcription factor and constitutes the main oxidative stress response in cells [13, 48]. Under the physiology condition, Nrf2 is located in the cytoplasm.…”

“…In addition to controlling neuronal hyperactivity and excitotoxicity, one important factor that should be dealt with is oxidative stress in epileptic seizures [10–12]. Oxidative stress means an imbalance between oxidation and antioxidation in vivo, which leads to excessive oxygen free radical and reduced antioxidative capacity [13–15]. Excessive oxygen free radical generated in SE dramatically impairs the structure and function of neurons [16–18].…”

“…Excessive oxygen free radical generated in SE dramatically impairs the structure and function of neurons [16–18]. Nuclear factor erythroid 2-related factor 2 (Nrf2), as a transcription factor, controls the basal and inducible expression of an array of antioxidant and detoxification enzymes to degrade oxygen free radical [13, 19, 20]. Disruption of Nrf2-antioxidant response elements (ARE) pathway results in an increased susceptibility to oxidative insults and other toxicants [21].…”

“…Disruption of Nrf2-antioxidant response elements (ARE) pathway results in an increased susceptibility to oxidative insults and other toxicants [21]. Activation of Nrf2-ARE pathway protects neurons against oxidative damage and excitotoxic damage [13, 22–24]. …”

Curcumin in epilepsy disorders

“…Nonetheless, curcumin may affect different growth and transcription factors, enzymes, and cytokines during its brief stay in the brain (Aggarwal et al, 2007). It is well known that curcumin is an inhibitor of nuclear factor κB and a potent inducer of heme oxygenase 1 protein (Carmona-Aparicio et al, 2015;Hill-Kapturczak, Thamilselvan, Liu, Nick, & Agarwal, 2001;Xie et al, 2017). Both of these factors play an essential role in inflammation and oxidative stress in the body.…”