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 (O-2(-)) 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/O-2(-)/ONOO- induced nitroxidative stress in neuronal and endothelial degeneration observed in Alzheimer's disease.