Is Nitric Oxide Assuming a Janus-Face in The Central Nervous System?

Abstract

Nitric Oxide, synthesized from L-arginine by the nitric oxide synthases, has a complex role within the human body. It contributes to almost every physiological system and has been found to be both protective and toxic in disease states. An aging population faces an increasing incidence of neurodegenerative disease and the pathological action of nitric oxide in Alzheimer's and Parkinson's diseases may be important therapeutic targets for the future. Nitric oxide's protective effects are also important to consider, through inhibition of caspase-3, nitrosylation of NMDA and increased activation of protein kinase B and CREB transcription factor. Nitric oxide has been shown to play a part in long term potentiation, revealing its importance in synaptic plasticity. Due to nitric oxide's mixed effects it is an exciting and varied therapeutic target. Currently, the impact of these therapies has been explored and developed in animal studies, but is yet to be fully realized in human trials. This paper outlines both the pathological and protective roles of nitric oxide in the central nervous system and the potential pharmacological therapies and targets these indicate.