The Nrf2 Pathway in Ischemic Stroke: A Review

Abstract

Ischemic stroke, characterized by the sudden loss of blood flow in specific area(s) of the brain, is the leading cause of permanent disability and is among the leading causes of death worldwide. The only approved pharmacological treatment for acute ischemic stroke (intravenous thrombolysis with recombinant tissue plasminogen activator) has significant clinical limitations and does not consider the complex set of events taking place after the onset of ischemic stroke (ischemic cascade), which is characterized by significant pro-oxidative events. The transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates the expression of a great number of antioxidant and/or defense proteins, has been pointed as a potential pharmacological target involved in the mitigation of deleterious oxidative events taking place at the ischemic cascade. This review summarizes studies concerning the protective role of Nrf2 in experimental models of ischemic stroke, emphasizing molecular events resulting from ischemic stroke that are, in parallel, modulated by Nrf2. Considering the acute nature of ischemic stroke, we discuss the challenges in using a putative pharmacological strategy (Nrf2 activator) that relies upon transcription, translation and metabolically active cells in treating ischemic stroke patients.

URB597 and Andrographolide Improve Brain Microvascular Endothelial Cell Permeability and Apoptosis by Reducing Oxidative Stress and Inflammation Associated with Activation of Nrf2 Signaling in Oxygen-Glucose Deprivation

“…There are some limitations to this study. Under stress conditions (excessive accumulation of ROS and inflammatory stress), Nrf2-Keap1 interaction is disrupted, and Nrf2 translocates into the nucleus encoding proteins (i.e., HO-1) that counterbalance impairments in inflammatory and redox control [ 55 ]. Therefore, it would be more helpful to confirm Nrf2 is mediating these vascular protective effects if nuclear translocation of Nrf2 was also accessed.…”

Ischemic stroke and dietary vitamin B12 deficiency in old-aged females impaired motor function, increased ischemic damage size, and changed metabolite profiles in brain and cecum tissue

“…The increased levels of oxidation lead to the activation of nuclear factor-erythroid factor 2-related factor (Nrf-2) (An et al, 2021), an important transcription factor involved in cellular response to oxidative stress. Ischemic stroke also results in oxidative stress and increased levels of Nrf-2 (Farina et al, 2021). In our previous study, we showed that supplementation with B vitamins, including vitamin B12, results in increased levels of Nrf-2 and superoxide dismutase 2 (SOD2) (Jadavji et al, 2017).…”

Ischemic Stroke and Dietary Vitamin B12 Deficiency in Old-Aged Females: Impaired Motor Function, Increased Ischemic Damage Size, and Changed Metabolite Profiles in Brain and Cecum Tissue

“…The increased levels of oxidation lead to the activation of nuclear factor–erythroid factor 2-related factor (Nrf-2) [ 43 ], an important transcription factor involved in the cellular response to oxidative stress. Ischemic stroke also results in oxidative stress and increased levels of Nrf-2 [ 44 ]. In our previous study, we showed that supplementation with B vitamins, including vitamin B12, results in increased levels of Nrf-2 and superoxide dismutase 2 (SOD2) [ 19 ].…”