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Neurotoxicity Research

, Volume 16, Issue 3, pp 293–305 | Cite as

Nitric Oxide as an Initiator of Brain Lesions During the Development of Alzheimer Disease

  • Gjumrakch Aliev
  • Hector H. Palacios
  • Amanda E. Lipsitt
  • Kathryn Fischbach
  • Bruce T. Lamb
  • Mark E. Obrenovich
  • Ludis Morales
  • Eldar Gasimov
  • Valentin Bragin
Article

Abstract

Nitric oxide (NO) is an important regulatory molecule for the host defense that plays a fundamental role in the cardiovascular, immune, and nervous systems. NO is synthesized through the conversion of l-arginine to l-citrulline by the enzyme NO synthase (NOS), which is found in three isoforms classified as neuronal (nNOS), inducible (iNOS), and endothelial (eNOS). Recent evidence supports the theory that this bioactive molecule has an influential role in the disruption of normal brain and vascular homeostasis, a condition known to elucidate chronic hypoperfusion which ultimately causes the development of brain lesions and the pathology that typify Alzheimer disease (AD). In addition, vascular NO activity appears to be a major contributor to this pathology before any overexpression of NOS isoforms is observed in the neuron, glia, and microglia of the brain tree, where the overexpression the NOS isoforms causes the formation of a large amount of NO. We hypothesize that since an imbalance between the NOS isoforms and endothelin-1 (ET-1), a human gene that encodes for blood vessel constriction, can cause antioxidant system insufficiency; by using pharmacological intervention with NO donors and/or NO suppressors, the brain lesions and the downstream progression of brain pathology and dementia in AD should be delayed or minimized.

Keywords

Alzheimer disease Nitric oxide Mitochondria Nitric oxide synthase Metabolism Oxidative stress 

Notes

Acknowledgments

Supported by grants from the Alzheimer Association and Philip Morris USA Research Management Groups.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Gjumrakch Aliev
    • 1
    • 2
    • 3
  • Hector H. Palacios
    • 1
  • Amanda E. Lipsitt
    • 4
  • Kathryn Fischbach
    • 1
  • Bruce T. Lamb
    • 5
  • Mark E. Obrenovich
    • 6
  • Ludis Morales
    • 2
  • Eldar Gasimov
    • 7
  • Valentin Bragin
    • 3
  1. 1.Department of Biology and Electron Microscopy Research CenterUniversity of Texas at San AntonioSan AntonioUSA
  2. 2.Department of Nutrition and Biochemistry, Faculty of SciencesJaveriana UniversityBogota D.CColombia
  3. 3.Stress Relief and Memory Training CenterBrooklyn, New YorkUSA
  4. 4.Department of Medicine, Division of Infectious DiseasesUniversity of Texas Health Science Center at San AntonioSan AntonioUSA
  5. 5.Department of NeuroscienceThe Lerner Research InstituteClevelandUSA
  6. 6.Department of PathologyCase Western Reserve UniversityClevelandUSA
  7. 7.Department of Cytology, Histology and EmbryologyAzerbaijan Medical UniversityBakuAzerbaijan

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