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Review Article

Exp Neurobiol 2017; 26(4): 195-205

Published online August 31, 2017

© The Korean Society for Brain and Neural Sciences

NOX Inhibitors - A Promising Avenue for Ischemic Stroke

Jong Youl Kim1, Joohyun Park1,2, Jong Eun Lee1,2* and Midori A. Yenari3*

1Department of Anatomy, Yensei University College of Medicine, 2BK21 Plus Project for Medical Sciences and Brain Research Institute, Yonsei University College of Medicine, Seoul 03722, Korea, 3Department of Neurology, University of California, San Francisco, and San Francisco Veterans Affairs Medical Center, San Francisco, California 94121, USA

Correspondence to: *To whom correspondence should be addressed.
Jong Eun Lee, TEL: 82-2-2228-1646, FAX: 82-2-365-0700
Midori A. Yenari, TEL: 1-415 750-2011, FAX: 1-415 750-2273

Received: July 27, 2017; Revised: August 9, 2017; Accepted: August 9, 2017


NADPH-oxidase (NOX) mediated superoxide originally found on leukocytes, but now recognized in several types of cells in the brain. It has been shown to play an important role in the progression of stroke and related cerebrovascular disease. NOX is a multisubunit complex consisting of 2 membrane-associated and 4 cytosolic subunits. NOX activation occurs when cytosolic subunits translocate to the membrane, leading to transport electrons to oxygen, thus producing superoxide. Superoxide produced by NOX is thought to function in long-term potentiation and intercellular signaling, but excessive production is damaging and has been implicated to play an important role in the progression of ischemic brain. Thus, inhibition of NOX activity may prove to be a promising treatment for ischemic brain as well as an adjunctive agent to prevent its secondary complications. There is mounting evidence that NOX inhibition in the ischemic brain is neuroprotective, and targeting NOX in circulating immune cells will also improve outcome. This review will focus on therapeutic effects of NOX assembly inhibitors in brain ischemia and stroke. However, the lack of specificity and toxicities of existing inhibitors are clear hurdles that will need to be overcome before this class of compounds could be translated clinically.

Keywords: ischemic stroke, NADPH oxidase, superoxide, NOX inhibition