Nitric oxide as an initiator of brain lesions during the development of Alzheimer disease.
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.
Aliev
Gjumrakch
G
Department of Biology and Electron Microscopy Research Center, University of Texas at San Antonio, San Antonio, TX 78249, USA. aliev03@gmail.com
Palacios
Hector H
HH
Lipsitt
Amanda E
AE
Fischbach
Kathryn
K
Lamb
Bruce T
BT
Obrenovich
Mark E
ME
Morales
Ludis
L
Gasimov
Eldar
E
Bragin
Valentin
V
D000544:Alzheimer Disease / Q000150:complications / Q000209:etiology / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000209:etiology* / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000503:physiopathology; D018450:Disease Progression; D019332:Endothelin-1 / Q000378:metabolism; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000145:classification / Q000378:metabolism; D018384:Oxidative Stress; D020033:Protein Isoforms / Q000378:metabolism
D019332:Endothelin-1; D020033:Protein Isoforms; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase