Cited by 279Redox biology and oxidative stressNitric Oxide and Endothelin EffectsNeutrophil, Myeloperoxidase and Oxidative Mechanisms

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New Insights on NOX Enzymes in the Central Nervous System

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Nayernia, Zeynab, Jaquet, Vincent, Krause, Karl-Heinz·2014·Antioxidants & Redox Signaling

DOI 10.1089/ars.2013.5703PMC PMC4026375

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Abstract

SIGNIFICANCE: There is increasing evidence that the generation of reactive oxygen species (ROS) in the central nervous system (CNS) involves the NOX family of nicotinamide adenine dinucleotide phosphate oxidases. Controlled ROS generation appears necessary for optimal functioning of the CNS through fine-tuning of redox-sensitive signaling pathways, while overshooting ROS generation will lead to oxidative stress and CNS disease. RECENT ADVANCES: NOX enzymes are not only restricted to microglia (i.e. brain phagocytes) but also expressed in neurons, astrocytes, and the neurovascular system. NOX enzymes are involved in CNS development, neural stem cell biology, and the function of mature neurons. While NOX2 appears to be a major source of pathological oxidative stress in the CNS, other NOX isoforms might also be of importance, for example, NOX4 in stroke. Globally speaking, there is now convincing evidence for a role of NOX enzymes in various neurodegenerative diseases, cerebrovascular diseases, and psychosis-related disorders. CRITICAL ISSUES: The relative importance of specific ROS sources (e.g., NOX enzymes vs. mitochondria; NOX2 vs. NOX4) in different pathological processes needs further investigation. The absence of specific inhibitors limits the possibility to investigate specific therapeutic strategies. The uncritical use of non-specific inhibitors (e.g., apocynin, diphenylene iodonium) and poorly validated antibodies may lead to misleading conclusions. FUTURE DIRECTIONS: Physiological and pathophysiological studies with cell-type-specific knock-out mice will be necessary to delineate the precise functions of NOX enzymes and their implications in pathomechanisms. The development of CNS-permeant, specific NOX inhibitors will be necessary to advance toward therapeutic applications.

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Authors: Nayernia, Z., Jaquet, V., & Krause, K.-H.
Affiliations: University of Geneva (CH)
Corresponding author: Krause, Karl-Heinz
ORCID: Jaquet, Vincent
Krause, Karl-Heinz
Venue: Antioxidants & Redox Signaling
Publisher: SAGE Publications
Published: 2014-06
Volume: 20
Issue: 17
Pages: 2815-2837
ISSN: 1523-0864 (ISSN-L)
1557-7716
DOI: 10.1089/ars.2013.5703
PMC: PMC4026375
OpenAlex: W2061260053
Cited by: 279
References: 194
Citations by year: 2026: 13 · 2025: 17 · 2024: 18 · 2023: 19 · 2022: 21 · 2021: 24 · 2020: 31 · 2019: 20 · 2018: 23 · 2017: 30 · 2016: 34 · 2015: 18 · 2014: 9
FWCI: 1.91
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Antioxidants and Redox Signaling (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Science Foundation (FP7/2007-2013)
European Commission (278611)
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (FP7/2007-2013, 141182, 310030B)
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, reactive oxygen species, central nervous system, oxidative stress, NOX2, NOX4, microglia, neurons, astrocytes, neurovascular system, neurodegenerative diseases, cerebrovascular disease, psychosis, stroke, redox signaling, NOX inhibitors
MeSH terms: Animals, Central Nervous System, Enzyme Inhibitors, Humans, Signal Transduction, Reactive Oxygen Species, Oxidative Stress, NADPH Oxidases, Neurodegenerative Diseases, Mice

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New Insights on NOX Enzymes in the Central Nervous System

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