Retinoic acid as a therapeutic option in Alzheimer's disease: a focus on cholinergic restoration

Retinoic acid is a potent cell differentiating factor, which through its nuclear receptors affects a vast range of promoter sites in brain neuronal and glial cells in every step of embryonic and postnatal life. Its capacities, facilitating maturation of neurotransmitter phenotype in different groups of neurons, pave the way for its application as a potential therapeutic agent in neurodegenerative diseases including Alzheimer's disease. Retinoic acid was found to exert particularly strong enhancing effects on acetylcholine transmitter functions in brain cholinergic neurons, loss of which is tightly linked to the development of cognitive and memory deficits in course of different cholinergic encephalopathies. Here, we review cholinotrophic properties of retinoic acid and its derivatives, which may justify their application in the management of Alzheimer's disease and the related neurodegenerative conditions.