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NADPH oxidase in brain injury and neurodegenerative disorders
Open accessAbstract
Oxidative stress is a common denominator in the pathology of neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis, as well as in ischemic and traumatic brain injury. The brain is highly vulnerable to oxidative damage due to its high metabolic demand. However, therapies attempting to scavenge free radicals have shown little success. By shifting the focus to inhibit the generation of damaging free radicals, recent studies have identified NADPH oxidase as a major contributor to disease pathology. NADPH oxidase has the primary function to generate free radicals. In particular, there is growing evidence that the isoforms NOX1, NOX2, and NOX4 can be upregulated by a variety of neurodegenerative factors. The majority of recent studies have shown that genetic and pharmacological inhibition of NADPH oxidase enzymes are neuroprotective and able to reduce detrimental aspects of pathology following ischemic and traumatic brain injury, as well as in chronic neurodegenerative disorders. This review aims to summarize evidence supporting the role of NADPH oxidase in the pathology of these neurological disorders, explores pharmacological strategies of targeting this major oxidative stress pathway, and outlines obstacles that need to be overcome for successful translation of these therapies to the clinic.
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“The robust activation of NOX isoforms in response to acute neuronal injury and chronic inflammation with oxidative damage has been well documented in post-mortem tissue and models of neurodegeneration (reviewed in [83]).”
From ROS Generation in Microglia: Understanding Oxidative Stress and Inflammation in Neurodegenerative Disease (2020) · cites this paper as [83]
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Metadata
- Authors
- Ma, M. W., Wang, J., Zhang, Q., Wang, R., Dhandapani, K. M., Vadlamudi, R. K., & Brann, D. W.
- Affiliations
- Augusta University (US)
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Brann, Darrell W.
- ORCID
- Venue
- Molecular Neurodegeneration
- Published
- 2017-01-17
- Volume
- 12
- Issue
- 1
- Pages
- 7-7
- ISSN
- 1750-1326 (ISSN-L)
- PMC
- PMC5240251
- OpenAlex
- W2574254633
- Cited by
- 432
- References
- 417
- Citations by year
- 2026: 21 · 2025: 45 · 2024: 43 · 2023: 59 · 2022: 44 · 2021: 67 · 2020: 49 · 2019: 38 · 2018: 40 · 2017: 26
- FWCI
- 3.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Molecular Neurodegeneration (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (5l101BX001117)
- National Institute of Neurological Disorders and Stroke (5R01NS050730, R01NS088058)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- NADPH oxidase, oxidative stress, neurodegenerative diseases, brain injury, ischemic brain injury, traumatic brain injury, NOX1, NOX2, NOX4, neuroprotection, antioxidant therapy, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis
- MeSH terms
- Animals, Brain Injuries, Humans, NADPH Oxidases, Neurodegenerative Diseases
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