Neuronal nicotinic acetylcholine receptors: from the genetic analysis to neurological diseases

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated channels that mediate, in the peripheral nervous system, fast neurotransmission at the neuromuscular junction and in ganglia. Widely expressed in the central nervous system neuronal nAChRs are thought to contribute both to neurotransmission and modulation of neuronal activity. To date, eleven genes encoding for these receptors have been identified in the mammalian genome and their structure is well conserved throughout evolution. Progresses made in the field of genetics and the identification of a large number of small genetic variants such as single nucleotide polymorphisms raise new questions about the physiologic and pharmacologic consequences of such variations. The finding of associations between polymorphisms in the genes encoding for the neuronal nAChRs and neurological disorders such as schizophrenia and Alzheimer disease illustrate the importance of getting a better understanding of these receptors from the gene to function. In this work we present an overview over the progress that has been made in understanding the role of nAChR genes in monogenic disorders such as familial epilepsy, and review the latest knowledge about genetic variants of the nAChR genes and their relationship with common disorders and behavioural traits of complex etiology.