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Published in:

01-10-2009

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

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

Published in: Neurotoxicity Research | Issue 3/2009

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.

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Title: Nitric Oxide as an Initiator of Brain Lesions During the Development of Alzheimer Disease
Authors: Gjumrakch Aliev
Hector H. Palacios
Amanda E. Lipsitt
Kathryn Fischbach
Bruce T. Lamb
Mark E. Obrenovich
Ludis Morales
Eldar Gasimov
Valentin Bragin
Publication date: 01-10-2009
Publisher: Springer-Verlag
Published in: Neurotoxicity Research / Issue 3/2009
Print ISSN: 1029-8428
Electronic ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-009-9066-5

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

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