TY - JOUR T1 - Understanding the bases of function and modulation of α7 nicotinic receptors: Implications for drug discovery JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.116.104240 SP - mol.116.104240 AU - Jeremias Corradi AU - Cecilia Bouzat Y1 - 2016/01/01 UR - http://molpharm.aspetjournals.org/content/early/2016/05/09/mol.116.104240.abstract N2 - The nicotinic acetylcholine receptor (nAChR) belongs to a superfamily of pentameric ligand gated ion channels involved in many physiological and pathological processes. Among nAChRs, receptors comprised of the α7 subunit are unique due to their high Ca2+ permeability and fast desensitization. nAChR agonists elicit a transient ion flux response that is further sustained by the release of calcium from intracellular sources. Due to the dual ionotropic/metabotropic nature of α7 receptors, signaling pathways are activated. The α7 subunit is highly expressed in the nervous system, mostly in regions implicated in cognition and memory, and has therefore attracted attention as a novel drug target. Additionally, its dysfunction is associated with several neuropsychiatric and neurological disorders, such as schizophrenia and Alzheimer's disease. α7 is also expressed in non-neuronal cells, particularly immune cells, where it plays a role in immunity, inflammation and neuroprotection. Thus, α7 potentiation has emerged as a therapeutic strategy for several neurological and inflammatory disorders. With unique activation properties, the receptor is a sensitive drug target carrying different potential binding sites for chemical modulators, particularly agonists and positive allosteric modulators. Although macroscopic and single-channel recordings have provided significant information underlying molecular mechanisms and binding sites of modulatory compounds, we know just the tip of the iceberg. Further concerted efforts are necessary to effectively exploit α7 as a drug target for each pathological situation. In this article, we focus mainly on the molecular basis of activation and drug modulation of α7, key pillars for rational drug design. ER -