Alzheimer's Disease: A Contextual Link with Nitric Oxide Synthase

Nitric oxide (NO) is a gasotransmitter with pleiotropic effects which has made a great impact on biology and medicine. A multidimensional neuromodulatory role of NO has been shown in the brain with specific reference to neurodegenerative disorders like Alzheimer's disease (AD) and cognitive dysfunction. It has been found that NO/cGMP signalling pathway has an important role in learning and memory. Initially, it was considered that indirectly NO exerted neurotoxicity in AD via glutamatergic excitotoxicity. However, considering the early development of cognitive functions involved in the learning memory process including long term potentiation and synaptic plasticity, NO has a crucial role. Increasing evidence uncovered the above facts that isoforms of NOS viz endothelial NO synthase (eNOS), neuronal NO synthase (nNOS) and inducible NO synthase (iNOS) having a variable expression in AD are mainly responsible for learning and memory activities. In this review, we focus on the role of NOS isoforms in AD parallel to NO. Further, this review provides convergent evidence that NO could provide a therapeutic avenue in AD via modulation of the relevant NOS expression.