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
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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