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Trends Mol Med. 2008 Mar;14(3):93-102. doi: 10.1016/j.molmed.2008.01.001. Epub 2008 Feb 11.

Nicotinic receptors, allosteric proteins and medicine.

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Research unit, National Center of Scientific Research 2182, Department of Neuroscience, Pasteur Institute, Paris, France.


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.

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