Role of nitric oxide in the vascular hypothesis of Alzheimer's disease

Abstract

Nitric oxide plays a fundamental role in the vascular hypothesis of Alzheimer's disease. The three subtypes of the enzyme nitric oxide synthase, responsible for the production of nitric oxide in the body, are involved in the pathophysiology of this disease. First, the decrease in vascular blood flow decreases the activation of the endothelial nitric oxide synthetase enzyme. Second, chronic inflammation resulting from senile plaque formation and microglial activation activates the inducible nitric oxide synthase enzyme. Third, alterations in calcium receptors increase the activation of the neuronal nitric oxide synthetase enzyme. Nitric oxide is also directly involved as it leads to an increase in oxidative / nitro-oxidative stress that alters mitochondrial function and leads to the eventual apoptosis of the cells of the neurovascular unit, causing the progressive cognitive and functional deterioration typical of the Alzheimer disease.