Neuronal nicotinic acetylcholine receptors: from the gene to the disease

Abstract

The neuronal nicotinic acetylcholine receptors are excitatory ligand-gated channels. Widely expressed throughout the peripheral and central nervous system, their properties depend upon their subunit composition. Furthermore, genetic studies have revealed a high degree of variation at the genomic level and alternative splicing of the mRNAs coding for these integral membrane proteins. In particular, genes coding for alpha4 and alpha7 subunits harbour a high degree of polymorphisms. Although well characterised at their molecular and functional level, the role of these receptors in the central nervous system remains obscure. Despite accumulating evidence for the participation of nicotinic receptors in disorders of the central nervous system including 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 heterogeneous, the investigation is difficult. However, in the past few years, significant progress has been made in understanding the contribution of nicotinic acetylcholine receptors to the origin of epilepsies and schizophrenia. By concentrating 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.