The role of nitric oxide in neurodegeneration. Potential for pharmacological intervention

Abstract

Nitric oxide (NO) is involved in important physiological functions of the CNS, including neurotransmission, memory and synaptic plasticity. Depending on the redox state of NO, it can act as a neurotoxin or it can have a neuroprotective action. Data suggest that NO may have a role in the pathogenesis of neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease. Additionally, these data indicate that inhibitors of the NO-synthesising enzyme, NO synthase, may be useful as neuroprotective agents in these diseases. In animal models, NOS inhibitors have been shown to prevent the neurotoxicity induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and other dopaminergic toxins. However, the clinical effects of NOS inhibitors remain unknown.