NADPH Oxidase: A Potential Target for Treatment of Stroke

Abstract

Stroke is the third leading cause of death in industrialized nations. Oxidative stress is involved in the pathogenesis of stroke, and excessive generation of reactive oxygen species (ROS) by mitochondria is thought to be the main cause of oxidative stress. NADPH oxidase (NOX) enzymes have recently been identified and studied as important producers of ROS in brain tissues after stroke. Several reports have shown that knockout or deletion of NOX exerts a neuroprotective effect in three major experimental stroke models. Recent studies also confirmed that NOX inhibitors ameliorate brain injury and improve neurological outcome after stroke. However, the physiological and pathophysiological roles of NOX enzymes in the central nervous system (CNS) are not known well. In this review, we provide a comprehensive summary of our current understanding about expression and physiological function of NOX enzymes in the CNS and its pathophysiological roles in the three major types of stroke: ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

Humanin analogue, S14G-humanin, has neuroprotective effects against oxygen glucose deprivation/reoxygenation by reactivating Jak2/Stat3 signaling through the PI3K/AKT pathway

“…Ischemia-induced deficiency of oxygen and glucose disrupt mitochondrial homeostasis and metabolism in brain neurons, resulting in the conversion of O 2 to O 2 . -(superoxide radical) and other reactive oxygen species (ROS) rather than utilization of O 2 for oxidative phosphorylation and adenosine triphosphate generation (25)(26)(27). Furthermore, blood reperfusion following ischemia leads to the activation of nicotinamide adenine dinucleotide phosphate oxidases, lipoxygenase and xanthine oxidase, all of which may produce ROS (25)(26)(27).…”

“…-(superoxide radical) and other reactive oxygen species (ROS) rather than utilization of O 2 for oxidative phosphorylation and adenosine triphosphate generation (25)(26)(27). Furthermore, blood reperfusion following ischemia leads to the activation of nicotinamide adenine dinucleotide phosphate oxidases, lipoxygenase and xanthine oxidase, all of which may produce ROS (25)(26)(27). Overproduction of ROS challenges the antioxidative system in neurons and poses oxidative damage to substances, such as lipids, that are rich in neurons but vulnerable to free radicals (25)(26)(27).…”

“…Furthermore, blood reperfusion following ischemia leads to the activation of nicotinamide adenine dinucleotide phosphate oxidases, lipoxygenase and xanthine oxidase, all of which may produce ROS (25)(26)(27). Overproduction of ROS challenges the antioxidative system in neurons and poses oxidative damage to substances, such as lipids, that are rich in neurons but vulnerable to free radicals (25)(26)(27). SOD represents an important antioxidant enzyme responsible for the elimination of O 2 .…”

Regulation of Hypertension for Secondary Prevention of Stroke: The Possible ‘Bridging Function' of Acupuncture

“…ROS constitute the most important factor for oxidative stress, and the major source of ROS is NADPH oxidase [54], which has been a potential target for the treatment of stroke [55]. Downregulation of nitrotyrosine protected neurons against ischemia injury [56].…”

Ischemia-reperfusion Injury in the Brain: Mechanisms and Potential Therapeutic Strategies

“…Another important source of ROS production is NADPH oxidase (NOX), a key component of electron transport chain in the plasma membrane, which generates free radicals by transferring one electron to molecular oxygen [13]. Experimental studies demonstrated that NOX2 gene deletion reduces BBB dysfunction and infarct size after filament MCAO for 2 h followed by reperfusion in mice [14], indicating the contribution of NOX in the pathogenesis of ischemia-reperfusion injury, and the potential of targeting NOX as a therapeutic strategy [15]. …”