Nrf2 as a therapeutic target in ischemic stroke

Mazur, Alexandra; Fangman, Madison; Ashouri, Rani; Arcenas, Arianna; Doré, Sylvain

doi:10.1080/14728222.2021.1890716

Cited by 19 publications

(10 citation statements)

References 16 publications

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“…In the quiescent state, Nrf2 is bound to Keap 1 (Kelch ECH associating protein 1) and inhibited. Subsequent to ROS attack or mediated through the proteinkinase C (PKC) pathway, MAPKs, or phosphoinositide 3-kinases (PI3Ks) [102], Keap 1 configuration changes and Nrf2 is uncoupled, being able to translocate to the nucleus, where it binds to ARE (antioxidant response element) and regulates the gene expression of antioxidant enzymes, growth factors, and anti-inflammatory proteins [103], as shown in Figure 2. The activation through the PI3K/Akt pathway occurs through inhibition of GSK-3β [104] and is triggered mainly by interleukin 4, which has been found significantly increased several hours after stroke [105].…”

Section: The Nrf2/are Signaling Pathwaymentioning

confidence: 99%

Oxidative Stress in Ischemia/Reperfusion Injuries following Acute Ischemic Stroke

Jurcău

Ardelean

2022

Biomedicines

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Recanalization therapy is increasingly used in the treatment of acute ischemic stroke. However, in about one third of these patients, recanalization is followed by ischemia/reperfusion injuries, and clinically to worsening of the neurological status. Much research has focused on unraveling the involved mechanisms in order to prevent or efficiently treat these injuries. What we know so far is that oxidative stress and mitochondrial dysfunction are significantly involved in the pathogenesis of ischemia/reperfusion injury. However, despite promising results obtained in experimental research, clinical studies trying to interfere with the oxidative pathways have mostly failed. The current article discusses the main mechanisms leading to ischemia/reperfusion injuries, such as mitochondrial dysfunction, excitotoxicity, and oxidative stress, and reviews the clinical trials with antioxidant molecules highlighting recent developments and future strategies.

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Section: The Nrf2/are Signaling Pathwaymentioning

confidence: 99%

Oxidative Stress in Ischemia/Reperfusion Injuries following Acute Ischemic Stroke

Jurcău

Ardelean

2022

Biomedicines

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“…With its crucial functions in heme and iron metabolism, glutathione restoration, antioxidant proliferation, thioredoxin, and protein turnover, Nrf2 plays a critical role in controlling excessive oxidative damage after ischemia [108,109]. Macrophages and microglia are the main Nrf2 suppliers in the nervous system [110,111].…”

Section: The Neuroprotective Effects Of Que On Strokementioning

confidence: 99%

Targeting Nrf2 signaling pathway by quercetin in the prevention and treatment of neurological disorders: An overview and update on new developments

Zamanian

Soltani

Khodarahmi

et al. 2023

Fundamemntal Clinical Pharma

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Background: Neurological disorders (NLDs) are widely acknowledged as a significant public health concern worldwide. Stroke, Alzheimer's disease (AD), and traumatic brain injury (TBI) are three of these disorders that have sparked major study attention. Neurological dysfunction, protein buildup, oxidation and neuronal injury, and aberrant mitochondria are all prevalent neuropathological hallmarks of these disorders. The signaling cascade of nuclear factor erythroid 2 related factor 2 (Nrf2) shares all of them as a common target. Several studies have found that overexpression of Nrf2 is a promising treatment method in NLDs. Effective treatment of these disorders continues to be a universal concern regardless of various medicines. In order to treat a variety of neurological problems, organic remedies may provide an alternative treatment. It has been demonstrated that polyphenols like quercetin (Que) offer considerable capabilities for treating NLDs. One of Que's greatest key targets, Nrf2, has the capacity to control the production of a number of cytoprotective enzymes that exhibit neuroprotective, detoxifying, and antioxidative effects. Additionally, Que enhanced the expression of Nrf2 and inhibited alterations in the shape and death of neurons in the hippocampus. Objective: In this review, we have focused on Que's medicinal prospects as a neuroprotective drug. Methods: PubMed, Scopus, Science Direct, and Google Scholar were used to search articles for this study. Results: The findings of this research demonstrate that (1) Que protected the blood‐brain barrier via stimulating Nrf2 in animal stroke, which alleviated ischemic reperfusion and motor dysfunction. (2) By triggering the Nrf2 pathway, Que reduced the neuroinflammation and oxidative damage brought on by TBI in the cortex. (3) In an experimental model of AD, Que enhanced cognitive function by decreasing A1‐4, antioxidant activity, and Nrf2 levels in the brain. Conclusion: We discuss recent research on Que‐mediated Nrf2 expression in the management of several NLDs in this paper.

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“…Furthermore, treatment with PRE-084 after the embolic stroke onset (3 and 24 hours) reduced the infarct volume significantly, inhibited proinflammatory cytokines, promoted anti-inflammatory cytokines (such as IL-10 and IL-4) [ 144 ]. Activation of the Nrf-2 antioxidant pathway another mechanism that benefits patients suffering with ischemic stroke [ 145 ], and activating it via the sigma-1 receptor using a sigma-1 receptor agonist such as fluvoxamine or cutamesine (SA4503) [ 146 ] could aid in stroke recovery as well as preventing further SARS-CoV-2 symptoms. Interestingly, the use of a sigma-1 receptor antagonist S1RA has also been shown to reduce damage caused by stroke and ameliorate post-stroke neurological deficits [ 147 ].…”

Section: The Role Of the Sigma-1 Receptor In Neurological Manifestations And Post-infection Related Neurological Diseasementioning

confidence: 99%

Drugs that offer the potential to reduce hospitalization and mortality from SARS-CoV-2 infection: The possible role of the sigma-1 receptor and autophagy

Brimson

Prasanth

Malar

et al. 2021

Expert Opinion on Therapeutic Targets

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Introduction: Despite the availability of new vaccines for SARS-CoV-2, there has been slow uptake and problems with supply in some parts of the world. Hence, there is still a necessity for drugs that can prevent hospitalization of patients and reduce the strain on health care systems. Drugs with sigma affinity potentially provide protection against the most severe symptoms of SARS-COV-2 and could prevent mortality via interactions with the sigma-1 receptor. Areas covered: This review examines the role of the sigma-1 receptor and autophagy in SARS-CoV-2 infections and how they may be linked. The authors reveal how sigma ligands may reduce the symptoms, complications, and deaths resulting from SARS-CoV-2 and offer insights on those patient cohorts that may benefit most from these drugs. Expert opinion: Drugs with sigma affinity potentially offer protection against the most severe symptoms of SARS-CoV-2 via interactions with the sigma-1 receptor. Agonists of the sigma-1 receptor may provide protection of the mitochondria, activate mitophagy to remove damaged and leaking mitochondria, prevent ER stress, manage calcium ion transport, and induce autophagy to prevent cell death in response to infection.

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Nrf2 as a therapeutic target in ischemic stroke

Cited by 19 publications

References 16 publications

Oxidative Stress in Ischemia/Reperfusion Injuries following Acute Ischemic Stroke

Oxidative Stress in Ischemia/Reperfusion Injuries following Acute Ischemic Stroke

Targeting Nrf2 signaling pathway by quercetin in the prevention and treatment of neurological disorders: An overview and update on new developments

Drugs that offer the potential to reduce hospitalization and mortality from SARS-CoV-2 infection: The possible role of the sigma-1 receptor and autophagy

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