Introduction of NADPH and Ischaemic Stroke

NADPH is the major reducing equivalent driving de novo synthesis of fatty acids, cholesterol, amino acids, and nucleotides. Its other major function is generation of superoxide (O2^-) by NADPH oxidases (NOXs) and scavenging of H2O2 by regenerating GSH and the antioxidant protein thioredoxin (TRX).

The NADPH oxidase family produces the transmembrane proteins responsible for transporting an electron from cytosolic NADPH across biological membranes, which reduces oxygen to superoxide anion. NADPH oxidase is the only oxidase that produces ROS. Regarding the central nervous system, NADPH oxidase-derived ROS are necessary for normal brain function, including neuronal differentiation and neuronal signaling, but overproduction of ROS contributes to nervous system disease.

Stroke is the leading cause of death and disability in humans. Excessive production of reactive oxygen species (ROS) is an important factor in oxidative stress and secondary brain damage after stroke. NADPH oxidase is thought to be a major source of ROS in the brain, and a large number of studies have demonstrated that knockdown of NADPH has a protective effect in models of ischaemic stroke.

Mechanisms of action

NADPH oxidase is the main producer of ROS and is widely distributed in the central nervous system. Following ischemic stroke, the expression of NOX subtypes increases sharply in cerebral vessels and neurons. Inhibiting the activity and expression of NOX may be an important starting point for ameliorating oxidative stress in ischemic stroke, although their precise roles have yet to be fully elucidated.

References:

[1] CHANDEL N S. NADPH-The Forgotten Reducing Equivalent.[J]. Cold Spring Harbor perspectives in biology, 2021, 13 6. DOI:10.1101/cshperspect.a040550.

[2] JINNAN DUAN. Pathophysiology and Therapeutic Potential of NADPH Oxidases in Ischemic Stroke-Induced Oxidative Stress.[J]. Oxidative Medicine and Cellular Longevity, 2021: 6631805. DOI:10.1155/2021/6631805.