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Cited by 356Neuroinflammation and Neurodegeneration MechanismsNitric Oxide and Endothelin EffectsNeurological Disease Mechanisms and Treatments

Implications of glial nitric oxide in neurodegenerative diseases

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Yuste, Jose Enrique, Tarragon, Ernesto, Campuzano, Carmen María, Ros-Bernal, Francisco·2015·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2015.00322PMC PMC4538301
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Abstract

Nitric oxide (NO) is a pleiotropic janus-faced molecule synthesized by nitric oxide synthases (NOS) which plays a critical role in a number of physiological and pathological processes in humans. The physiological roles of NO depend on its local concentrations, as well as its availability and the nature of downstream target molecules. Its double-edged sword action has been linked to neurodegenerative disorders. Excessive NO production, as the evoked by inflammatory signals, has been identified as one of the major causative reasons for the pathogenesis of several neurodegenerative diseases. Moreover, excessive NO synthesis under neuroinflammation leads to the formation of reactive nitrogen species and neuronal cell death. There is an intimate relation between microglial activation, NO and neuroinflammation in the human brain. The role of NO in neuroinflammation has been defined in animal models where this neurotransmitter can modulate the inflammatory process acting on key regulatory pathways, such as those associated with excitotoxicity processes induced by glutamate accumulation and microglial activation. Activated glia express inducible NOS and produce NO that triggers calcium mobilization from the endoplasmic reticulum, activating the release of vesicular glutamate from astroglial cells resulting in neuronal death. This change in microglia potentially contributes to the increased age-associated susceptibility and neurodegeneration. In the current review, information is provided about the role of NO, glial activation and age-related processes in the central nervous system (CNS) that may be helpful in the isolation of new therapeutic targets for aging and neurodegenerative diseases.

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  • Continuous activation of microglia can lead to the over-production of inflammatory cytokines, as identified in postmortem brains of Alzheimer's and Parkinson's disease patients.

    “However, continuous activation of microglia can lead to the over-production of inflammatory cytokines, as identified in postmortem brains of Alzheimer’s and Parkinson’s disease patients [49].”

    From Polyphenol Microbial Metabolites Exhibit Gut and Blood–Brain Barrier Permeability and Protect Murine Microglia against LPS-Induced Inflammation (2019) · cites this paper as [49]

    The Parkinson’s Disease section (page unavailable) reports elevated inflammatory cytokines in postmortem brains of PD patients and links chronic inflammation to activated microglia and astroglia. The Alzheimer’s Disease section links amyloid plaques to production of inflammatory cytokines, but does not identify cytokine overproduction in postmortem AD brains. The source therefore does not support the claim’s postmortem finding for both diseases. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • iNOS is expressed in both microglia and astrocytes.

    “iNOS is expressed in both microglia and astrocytes.453”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [453]

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Authors
Yuste, J. E., Tarragon, E., Campuzano, C. M., & Ros-Bernal, F.
Affiliations
Universitat Jaume I (ES)
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2015-08-17
Volume
9
Pages
322-322
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2015.00322
PMC
PMC4538301
OpenAlex
W1584106444
Cited by
356
References
167
Citations by year
2026: 26 · 2025: 32 · 2024: 25 · 2023: 30 · 2022: 45 · 2021: 45 · 2020: 36 · 2019: 25 · 2018: 33 · 2017: 28 · 2016: 28 · 2015: 1
FWCI
2.39
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Repositori UJI (Universitat Jaume I) (submittedVersion, cc-by-sa)
Funders
  • Ministerio de Ciencia e Innovación (SAF 2007-62262)
  • Université de Liège
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
nitric oxide, neurodegenerative diseases, neuroinflammation, microglial activation, astrocytes, inducible nitric oxide synthase, reactive nitrogen species, excitotoxicity, glutamate, neuronal cell death, aging, therapeutic target

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