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NADPH Oxidase as a Therapeutic Target for Neuroprotection against Ischaemic Stroke: Future Perspectives
Stroke Injury and Repair Team, O'Brien Institute, St Vincent's Hospital, 42 Fitzroy St, Fitzroy, Melbourne 3065, Australia
Florey Neuroscience Institutes, Melbourne Brain Centre, 245 Burgundy St, Heidelberg 3084, Australia
Department of Medicine, University of Melbourne, St Vincent's Campus, Melbourne 3065, Australia
* Author to whom correspondence should be addressed.
Received: 31 January 2013; in revised form: 14 March 2013 / Accepted: 20 March 2013 / Published: 22 April 2013
Abstract: Oxidative stress caused by an excess of reactive oxygen species (ROS) is known to contribute to stroke injury, particularly during reperfusion, and antioxidants targeting this process have resulted in improved outcomes experimentally. Unfortunately these improvements have not been successfully translated to the clinical setting. Targeting the source of oxidative stress may provide a superior therapeutic approach. The NADPH oxidases are a family of enzymes dedicated solely to ROS production and pre-clinical animal studies targeting NADPH oxidases have shown promising results. However there are multiple factors that need to be considered for future drug development: There are several homologues of the catalytic subunit of NADPH oxidase. All have differing physiological roles and may contribute differentially to oxidative damage after stroke. Additionally, the role of ROS in brain repair is largely unexplored, which should be taken into consideration when developing drugs that inhibit specific NADPH oxidases after injury. This article focuses on the current knowledge regarding NADPH oxidase after stroke including in vivo genetic and inhibitor studies. The caution required when interpreting reports of positive outcomes after NADPH oxidase inhibition is also discussed, as effects on long term recovery are yet to be investigated and are likely to affect successful clinical translation.
Keywords: brain injury; cerebrovascular event; reactive oxygen species; Nox; brain repair; drug development; inhibitors; ischaemic stroke
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MDPI and ACS Style
McCann, S.K.; Roulston, C.L. NADPH Oxidase as a Therapeutic Target for Neuroprotection against Ischaemic Stroke: Future Perspectives. Brain Sci. 2013, 3, 561-598.
McCann SK, Roulston CL. NADPH Oxidase as a Therapeutic Target for Neuroprotection against Ischaemic Stroke: Future Perspectives. Brain Sciences. 2013; 3(2):561-598.
McCann, Sarah K.; Roulston, Carli L. 2013. "NADPH Oxidase as a Therapeutic Target for Neuroprotection against Ischaemic Stroke: Future Perspectives." Brain Sci. 3, no. 2: 561-598.