Nicotinic receptors, allosteric proteins and medicine.
The nicotinic acetylcholine receptor (nAChR) was the first ion channel and membrane receptor of a neurotransmitter to be isolated and chemically identified and is one of the best known membrane proteins involved in signal transduction. Subsequently, nAChRs have been a target for drug discovery because of their potential to impact numerous brain diseases and disorders. Here, we consider recent developments in our understanding of nAChR structure and of the conformational transitions that link the acetylcholine (ACh)-binding site and the ion channel to mediate fast neurotransmission. The knowledge of such allosteric mechanisms is essential to understand pathologies such as congenital myasthenia, autosomal dominant nocturnal frontal lobe epilepsies, sudden infant death syndrome, attention deficit hyperactivity disorder and nicotine addiction and to design novel therapies.
Changeux
Jean-Pierre
JP
Research unit, National Center of Scientific Research 2182, Department of Neuroscience, Pasteur Institute, Paris, France. changeux@pasteur.fr
Taly
Antoine
A
D000109:Acetylcholine / Q000378:metabolism; D000494:Allosteric Regulation; D000495:Allosteric Site / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D007223:Infant; D009422:Nervous System Diseases / Q000378:metabolism; D018722:Nicotinic Agonists / Q000737:chemistry / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry; D017981:Receptors, Neurotransmitter / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013398:Sudden Infant Death / Q000209:etiology
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D021122:Protein Subunits; D017981:Receptors, Neurotransmitter; D011978:Receptors, Nicotinic; D000109:Acetylcholine