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Cited by 373Redox biology and oxidative stressNitric Oxide and Endothelin EffectsNeutrophil, Myeloperoxidase and Oxidative Mechanisms

The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders

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Tarafdar, Anuradha, Pula, Giordano·2018·International Journal of Molecular Sciences
DOI 10.3390/ijms19123824PMC PMC6321244
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Abstract

For a number of years, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) was synonymous with NOX2/gp91phox and was considered to be a peculiarity of professional phagocytic cells. Over the last decade, several more homologs have been identified and based on current research, the NOX family consists of NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2 enzymes. NOXs are electron transporting membrane proteins that are responsible for reactive oxygen species (ROS) generation—primarily superoxide anion (O2●−), although hydrogen peroxide (H2O2) can also be generated. Elevated ROS leads to oxidative stress (OS), which has been associated with a myriad of inflammatory and degenerative pathologies. Interestingly, OS is also the commonality in the pathophysiology of neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). NOX enzymes are expressed in neurons, glial cells and cerebrovascular endothelial cells. NOX-mediated OS is identified as one of the main causes of cerebrovascular damage in neurodegenerative diseases. In this review, we will discuss recent developments in our understanding of the mechanisms linking NOX activity, OS and neurodegenerative diseases, with particular focus on the neurovascular component of these conditions. We conclude highlighting current challenges and future opportunities to combat age-related neurodegenerative disorders by targeting NOXs.

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  • Oxidative stress is a significant biomarker common to the pathophysiology of both AD and PD.

    “Oxidative stress is associated with a number of inflammatory and degenerative pathologies and is a significant biomarker common to the pathophysiology of both AD and PD. 55 , 58”

    From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [55]

    Section 5, “Oxidative Stress and Dementia” (page unavailable), calls oxidative stress a key mediator in the pathogenesis of both AD and PD. That supports its common pathogenic role, but the passage does not identify oxidative stress as a biomarker of either disease. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Age-related alterations in the brain microenvironment lead to increased BBB permeability and leakiness, neuronal degeneration, production of reactive oxygen species and inflammation.

    “Age‐related alterations in the brain microenvironment gradually led to increased BBB permeability and leakiness, neuronal degeneration, production of reactive oxygen species (ROS) and inflammation. 54 , 55 , 56”

    From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [55]

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Cited by

Sorted by citations

Authors
Tarafdar, A., & Pula, G.
Affiliations
University of Exeter (GB)
Corresponding author
Tarafdar, Anuradha
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2018-11-30
Volume
19
Issue
12
Pages
3824
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms19123824
PMC
PMC6321244
OpenAlex
W2902683674
Cited by
373
References
27
Citations by year
2026: 25 · 2025: 50 · 2024: 44 · 2023: 60 · 2022: 69 · 2021: 65 · 2020: 35 · 2019: 25
FWCI
3.06
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Alzheimer's Research UK (3858)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords
NADPH oxidase, oxidative stress, neurodegenerative diseases, reactive oxygen species, superoxide, hydrogen peroxide, NOX1, NOX4, DUOX1, DUOX2, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, neurovascular unit, cerebrovascular injury, glial cells, endothelial cells, age-related neurodegeneration
MeSH terms
Animals, Humans, Amyloid beta-Peptides, Reactive Oxygen Species, Oxidative Stress, NADPH Oxidases, Neurodegenerative Diseases

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