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

Research output: Contribution to journalArticle

83 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)293-305
Number of pages13
JournalNeurotoxicity Research
Volume16
Issue number3
DOIs
StatePublished - Jun 5 2009

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Keywords

  • Alzheimer disease
  • Metabolism
  • Mitochondria
  • Nitric oxide
  • Nitric oxide synthase
  • Oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Aliev, G., Palacios, H. H., Lipsitt, A. E., Fischbach, K., Lamb, B. T., Obrenovich, M. E., Morales, L., Gasimov, E., & Bragin, V. (2009). Nitric oxide as an initiator of brain lesions during the development of Alzheimer disease. Neurotoxicity Research, 16(3), 293-305. https://doi.org/10.1007/s12640-009-9066-5