Nitric Oxide Mimetic Molecules as Therapeutic Agents in Alzheimers Disease

Gregory   R.J.   Thatcher; Brian   M.   Bennett; James   N.   Reynolds

Abstract

Nitric oxide is multifunctional messenger molecule in the brain, playing important roles including in learning and memory and in regulating the expression of trophic factors that may be reduced with aging. Small molecules that mimic the biological activity of NO, NO mimetics, will bypass cholinergic receptor activation and are anticipated to provide multiple pathways of treating and circumventing dementia in Alzheimers disease. Activation of soluble guanylyl cyclase and cGMP formation in the brain represents one element of effective neuroprotective pathways mediated by NO. Substantial evidence suggests that NO mimetics may display cGMP-dependent and cGMP-independent activity and may operate via multiple biochemical signaling pathways, both to ensure the survival of neurons subjected to stress and also to provide cognition-enabling pathways to circumvent dementia. GT 1061 is an NO mimetic compound currently in clinical trials for Alzheimers. A survey of current research indicates that NO mimetics will provide a combined neuroprotective and cognition-enabling approach to anti-neurodegenerative therapy.

Keywords: cognition, dementia, nitric oxide, cgmp, nitrate, alzheimers, neurodegeneration, bdnf