NeuroCypres: Neurotransmitter Cys-loop receptors: structure, function and disease.

Neurocypres is a large-scale integrated project involving 20 European laboratories in the area of Cys-loop neurotransmitter receptors funded by the European Union as of February 1, 2008. In the seventh research framework programme (FP7), the EU commission devoted a special call to stimulate high-throughput approaches to structure function analyses of membrane-transporters and channels for the identification of potential new drug target sites. The Neurocypres consortium (Neurotransmitter Cys-loop receptors: structure, function and disease) is devoted to studying structural and functional aspects of Cys-loop receptors, a superfamily of ligand-gated ion channels. Cys-loop receptors (CLRs) share a generic protein architecture consisting of five subunits with an integral ion-channel that can open and close depending on ligand binding. The group comprises nicotinic acetylcholine-, GABAA-, 5HT3-, and Glycine receptors, which all have important roles in central and peripheral nervous system function. CLRs are crucial to the function of the peripheral and central nervous system. Dysfunction of CLRs is linked to muscle disorders (e.g. myasthenic syndromes), hyperexcitabiliy of the brain (e.g. epilepsy) and spinal cord (e.g. hyperekplexia / stiff baby syndrome) as well as nicotine addiction, while CLR subunit genes serve as candidates for frequent psychiatric diseases (e.g. schizophrenia). Moreover, CLRs serve as molecular targets for a functionally diverse group of clinically important drugs, including curare-like muscle relaxants, tranquillizers and anticonvulsants like the benzodiazepines, as well as anti-emetics. Based on the identification of selective CLR subtypes, novel drugs are on the horizon, mediating highly selective therapeutic effects and providing new avenues for therapeutically use.

Keywords:Ligand-gated ion channels, Cys-loop receptors, GABA-A receptors, nAChRs, Glycine receptors, 5HT3 receptors, X-ray crystallography

Disciplines:Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing