Neuronal nicotinic acetylcholine receptors: from the gene to the disease

The neuronal nicotinic acetylcholine receptors are excitatory ligand-gated channels. Widely expressed throughout the peripheral and central nervous sy stem, their properties depend upon their subunit composition. Furthermore, genetic studies have revealed a high degree of variation at the genomic lev el and alternative splicing of the mRNAs coding for these integral membrane proteins. In particular, genes coding for alpha 4 and alpha 7 subunits har bour a high degree of polymorphisms. Although well characterised at their m olecular and functional level, the role of these receptors in the central n ervous system remains obscure. Despite accumulating evidence for the partic ipation of nicotinic receptors in disorders of the central nervous system i ncluding nicotinic addiction, Parkinson's disease, Alzheimer's disease and Tourette's syndrome, the exact role of these receptors is still speculative . Because most of these phenotypes are complex and genetically heterogeneou s, the investigation is difficult. However, in the past few years, signific ant progress has been made in understanding the contribution of nicotinic a cetylcholine receptors to the origin of epilepsies and schizophrenia. By co ncentrating on the latest results gained for these diseases, we discuss in this review the possible relationships between neuronal nicotinic receptors and neurological and psychiatric disorders. (C) 2000 Elsevier Science B.V. All rights reserved.