Nitric oxide and nitroxidative stress in Alzheimer's disease.
Nitric oxide is a signaling molecule produced by neurons and endothelial cells in the brain. NO is synthesized from L-arginine and oxygen by nitric oxide synthase: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). The endothelial NO acts as a vasorelaxant in the vasculature and as a neurotransmitter when produced by neurons (under the pathological conditions of Alzheimer's disease). NO can be scavenged in a rapid reaction with superoxide (O2-) to generate peroxynitrite (ONOO-), with a half-life of < 1 s. ONOO- is a potent oxidant and the primary component of nitroxidative stress. At high concentrations (> 100 nM), ONOO- can undergo homolytic or heterolytic cleavage to produce NO2+, NO2, and OH., highly reactive oxidative species and secondary components of nitroxidative stress. The high nitroxidative stress can initiate a cascade of redox reactions which can trigger apoptosis and evoke cytotoxic effects on neurons and endothelial cells. This article reviews the functions of NO and the potential role of NO/O2-/ONOO- induced nitroxidative stress in neuronal and endothelial degeneration observed in Alzheimer's disease.
Malinski
Tadeusz
T
Department of Chemistry and Biochemistry Ohio University, 350 W. State Street, Athens, OH 45701, USA. malinski@ohio.edu
D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity; D017209:Apoptosis / Q000502:physiology; D020372:Dexfenfluramine; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D030421:Peroxynitrous Acid / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D016229:Amyloid beta-Peptides; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D020372:Dexfenfluramine