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IBRO Rep. 2019 Aug 1;7:59-69. doi: 10.1016/j.ibror.2019.07.1721. eCollection 2019 Dec.

The role of NOX inhibitors in neurodegenerative diseases.

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Department of Anatomy, College of Medicine, Yonsei University, Republic of Korea.
Department of Neurology, San Francisco Veterans Affairs Medical Center, University of California, San Francisco, 4150 Clement Street, MS 127, San Francisco, CA, 94121, United States.
Brain Korea 21, PLUS Project for Medical Science, College of Medicine, Yonsei University, Republic of Korea.
Brain Research Institute, College of Medicine, Yonsei University, Republic of Korea.


Oxidative stress is a key player in both chronic and acute brain disease due to the higher metabolic demand of the brain. Among the producers of free radicals, NADPH-oxidase (NOX) is a major contributor to oxidative stress in neurological disorders. In the brain, the superoxide produced by NOX is mainly found in leukocytes. However, recent studies have reported that it can be found in several other cell types. NOX has been reported to regulate neuronal signaling, memory processing, and central cardiovascular homeostasis. However, overproduction of NOX can contribute to neurotoxicity, CNS degeneration, and cardiovascular disorders. Regarding the above functions, NOX has been shown to play a crucial role in chronic CNS diseases like Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), and in acute CNS disorders such as stroke, spinal cord injury, traumatic brain injury (TBI), and related cerebrovascular diseases. NOX is a multi-subunit complex consisting of two membrane-associated and four cytosolic subunits. Thus, in recent years, inhibition of NOX activity has drawn a great deal of attention from researchers in the field of treating chronic and acute CNS disorders and preventing secondary complications. Mounting evidence has shown that NOX inhibition is neuroprotective and that inhibiting NOX in circulating immune cells can improve neurological disease conditions. This review summarizes recent studies on the therapeutic effects and pharmacological strategies regarding NOX inhibitors in chronic and acute brain diseases and focuses on the hurdles that should be overcome before their clinical implementation.


Ischemic stroke; NADPH oxidase; NOX inhibition; Superoxide

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