The neuroprotective effects of apocynin

Simonyi, Ágnes

doi:10.2741/e535

Cited by 56 publications

(19 citation statements)

References 77 publications

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“…Therefore, inhibiting the production of ROS is an effective method for treatment of oxidative stress injuries and explains the neuroprotective role of NOX inhibitors (28), including gp91ds-tat and apocynin (29,30). These results suggest that NOX2/4 are potential targets for antioxidant therapy.…”

Section: Discussionmentioning

confidence: 99%

Role of ALK5/SMAD2/3 signaling in the regulation of NOX expression in cerebral ischemia/reperfusion injury

et al. 2018

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Nicotinamide adenine dinucleotide phosphate oxidase (NOX)-derived reactive oxygen species (ROS) serve an important role in cerebral ischemia/reperfusion (I/R) injury. However, the mechanism by which ROS generation is regulated has not yet been fully elucidated. The present study aimed to explore the role of transforming growth factor-β signaling in ROS generation. Sprague Dawley rats were subjected to I/R injury and PC-12 cells were transfected with small interfering RNA against activin receptor-like kinase (ALK)5 or hypoxia/reoxygenation (H/R). The results indicated that I/R or H/R significantly increased ALK5 expression, SMAD2/3 phosphorylation and NOX2/4 expression and activity, concomitant with ROS generation and apoptosis. In addition, ALK5 knockdown significantly reversed changes induced by H/R treatment in PC-12 cells. These results suggest that ALK5/SMAD2/3 signaling serves a key role in oxidative stress. To the best of our knowledge, this is the first study to demonstrate that ALK5/SMAD2/3 activation is associated with the regulation of NOX2/4 expression and exacerbates I/R injury.

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Section: Discussionmentioning

confidence: 99%

Role of ALK5/SMAD2/3 signaling in the regulation of NOX expression in cerebral ischemia/reperfusion injury

et al. 2018

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“…The interpretation of studies using apocynin is further complicated by its antioxidant capacity (25) and inhibition of Rho kinase (52). Thus, classical NOX inhibitors are not specific for NADPH oxidases, and, therefore, any results on the role of NADPH oxidase obtained by using apocynin or DPI should be questioned (43,57,69,71). A more specific NOX inhibitor is the triazolopyrimidine VAS2870 (Fig.…”

Section: Role Of Nox4 In Strokementioning

confidence: 99%

Neuroprotection After Stroke by Targeting NOX4 As a Source of Oxidative Stress

Radermacher

Wingler

Langhauser

et al. 2013

Antioxidants & Redox Signaling

126

107

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Significance: Stroke, a leading cause of death and disability, poses a substantial burden for patients, relatives, and our healthcare systems. Only one drug is approved for treating stroke, and more than 30 contraindications exclude its use in 90% of all patients. Thus, new treatments are urgently needed. In this review, we discuss oxidative stress as a pathomechanism of poststroke neurodegeneration and the inhibition of its source, type 4 nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX4), as a conceptual breakthrough in stroke therapy. Recent Advances: Among potential sources of reactive oxygen species (ROS), the NOXes stand out as the only enzyme family that is solely dedicated to forming ROS. In rodents, three cerebrovascular NOXes exist: the superoxide-forming NOX1 and 2 and the hydrogen peroxide-forming NOX4. Studies using NOX1 knockout mice gave conflicting results, which overall do not point to a role for this isoform. Several reports find NOX2 to be relevant in stroke, albeit to variable and moderate degrees. In our hands, NOX4 is, by far, the major source of oxidative stress and neurodegeneration on ischemic stroke. Critical Issues: We critically discuss the tools that have been used to validate the roles of NOX in stroke. We also highlight the relevance of different animal models and the need for advanced quality control in preclinical stroke research. Future Directions: The development of isoform-specific NOX inhibitors presents a precious tool for further clarifying the role and drugability of NOX homologues. This could pave the avenue for the first clinically effective neuroprotectant applied poststroke, and even beyond this, stroke could provide a proof of principle for antioxidative stress therapy.

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“…Some traditional herbal antioxidants also exhibit potential for AD treatment. Apocynin, a constituent of the Himalayan medicinal herb Picrorhiza kurroa, has been reported to exhibit anti-AD effects through NADPH-oxidase inhibition to suppress ROS and reactive nitrogen species [281].…”

Section: Antioxidantsmentioning

confidence: 99%

Slow Excitotoxicity in Alzheimer's Disease

Ong

Tanaka

Dawe

et al. 2013

JAD

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Abstract. Progress is being made in identifying possible pathogenic factors and novel genes in the development of Alzheimer's disease (AD). Many of these could contribute to 'slow excitotoxicity', defined as neuronal loss due to overexcitation as a consequence of decreased energy production due, for instance, to changes in insulin receptor signaling; or receptor abnormalities, such as tau-induced alterations in N-methyl-D-aspartate (NMDA) receptor phosphorylation. As a result, glutamate becomes neurotoxic at concentrations that normally show no toxicity. In AD, NMDA receptors are overexcited by glutamate in a tonic, rather than a phasic manner. Moreover, in prodromal AD subjects, functional MRI reveals an increase in neural network activities relative to baseline, rather than loss of activity. This may be an attempt to compensate for reduced number of neurons, or reflect ongoing slow excitotoxicity. This article reviews possible links between AD pathogenic factors such as A␤PP/A␤ and tau; novel risk genes including clusterin, phosphatidylinositol-binding clathrin assembly protein, complement receptor 1, bridging integrator 1, ATP-binding cassette transporter 7, membrane-spanning 4-domains subfamily A, CD2-associated protein, sialic acid-binding immunoglobulin-like lectin, and ephrin receptor A1; metabolic changes including insulin resistance and hypercholesterolemia; lipid changes including alterations in brain phospholipids, cholesterol and ceramides; glial changes affecting microglia and astrocytes; alterations in brain iron metallome and oxidative stress; and slow excitotoxicity. Better understanding of the possible molecular links between pathogenic factors and slow excitotoxicity could inform our understanding of the disease, and pave the way towards new therapeutic strategies for AD.

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The neuroprotective effects of apocynin

Cited by 56 publications

References 77 publications

Role of ALK5/SMAD2/3 signaling in the regulation of NOX expression in cerebral ischemia/reperfusion injury

Role of ALK5/SMAD2/3 signaling in the regulation of NOX expression in cerebral ischemia/reperfusion injury

Neuroprotection After Stroke by Targeting NOX4 As a Source of Oxidative Stress

Slow Excitotoxicity in Alzheimer's Disease

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