CNS NICOTINIC RECEPTORS - POSSIBLE THERAPEUTIC TARGETS IN NEURODEGENERATIVE DISORDERS

CNS nicotinic acetylcholine receptors are a family of ligand-gated cat ion channels that allow the passage of calcium ions. They are structur ally and functionally distinct from nicotinic receptors at the neuromu scular junction, CNS nicotinic receptors show a variation in distribut ion and pharmacology. The number of these receptors is reduced with no rmal aging, and a further reduction in number occurs in dementing cond itions that err common in elderly individuals. A comparison of recepto r loss in the substantia nigra of patients with Parkinson's disease an d Lewy body dementia indicates that this process may occur early in th e disease and precede cell loss. In addition, nicotine binding sites i n humans are concentrated in the entorhinal cortex and subicular forma tion, areas that are affected early in the course of Alzheimer-type di sease. The number of nicotine binding sites is high in human neonatal brain, at which stage exposure to nicotine and tobacco smoke is delete rious. Conversely, epidemiological evidence suggests that later in lif e tobacco smoking may offer some protection against Parkinson's and Al zheimer's diseases. Exposure to nicotinic agonists and tobacco smoke i ncreases the number of brain nicotinic receptors both in humans and ex perimental animals, although the functional significance of this and i ts precise relationship to receptor desensitisation is not completely understood. Acute exposure to nicotine and nicotinic antagonists has b eneficial and adverse effects, respectively, on cognitive function. Su bcutaneous administration of nicotine to patients with Alzheimer's dis ease improves discriminative sensitivity and reaction times. Available nicotinic agonists appear to induce diverse functional responses, and models for the testing of such novel compounds are needed.