Pathophysiology and Treatments of Oxidative Injury in Ischemic Stroke: Focus on the Phagocytic NADPH Oxidase 2
Autor: | François Mach, Fabrizio Montecucco, Nicolas Vuilleumier, Federico Carbone, Vincent Braunersreuther, Priscila Camillo Teixeira |
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Rok vydání: | 2015 |
Předmět: |
Azoles
Enzyme complex Physiology Clinical Biochemistry Isoindoles medicine.disease_cause Biochemistry Antioxidants chemistry.chemical_compound 0302 clinical medicine Organoselenium Compounds Edaravone Medicine Stroke General Environmental Science ddc:616 chemistry.chemical_classification 0303 health sciences Membrane Glycoproteins NADPH oxidase biology Brain Forum Review Articles 3. Good health Respiratory burst NADPH Oxidase 2 Oxidation-Reduction Signal Transduction Neuroprotection 03 medical and health sciences Phagocytosis Animals Humans Molecular Biology 030304 developmental biology Reactive oxygen species business.industry NADPH Oxidases Cell Biology medicine.disease Oxidative Stress chemistry Immunology biology.protein General Earth and Planetary Sciences Reactive Oxygen Species business Antipyrine 030217 neurology & neurosurgery Oxidative stress |
Zdroj: | Antioxidants & Redox Signaling Antioxidants & Redox Signaling, Vol. 23, No 5 (2015) pp. 460-489 Antioxidants & redox signaling |
ISSN: | 1557-7716 1523-0864 |
Popis: | Significance: Phagocytes play a key role in promoting the oxidative stress after ischemic stroke occurrence. The phagocytic NADPH oxidase (NOX) 2 is a membrane-bound enzyme complex involved in the antimicrobial respiratory burst and free radical production in these cells. Recent Advances: Different oxidants have been shown to induce opposite effects on neuronal homeostasis after a stroke. However, several experimental models support the detrimental effects of NOX activity (especially the phagocytic isoform) on brain recovery after stroke. Therapeutic strategies selectively targeting the neurotoxic ROS and increasing neuroprotective oxidants have recently produced promising results. Critical Issues: NOX2 might promote carotid plaque rupture and stroke occurrence. In addition, NOX2-derived reactive oxygen species (ROS) released by resident and recruited phagocytes enhance cerebral ischemic injury, activating the inflammatory apoptotic pathways. The aim of this review is to update evidence on phagocyte-related oxidative stress, focusing on the role of NOX2 as a potential therapeutic target to reduce ROS-related cerebral injury after stroke. Future Directions: Radical scavenger compounds (such as Ebselen and Edaravone) are under clinical investigation as a therapeutic approach against stroke. On the other hand, NOX inhibition might represent a promising strategy to prevent the stroke-related injury. Although selective NOX inhibitors are not yet available, nonselective compounds (such as apocynin and fasudil) provided encouraging results in preclinical studies. Whereas additional studies are needed to better evaluate this therapeutic potential in human beings, the development of specific NOX inhibitors (such as monoclonal antibodies, small-molecule inhibitors, or aptamers) might further improve brain recovery after stroke. Antioxid. Redox Signal. 23, 460–489. |
Databáze: | OpenAIRE |
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