1. The nicotinic receptor alpha5 coding polymorphism rs16969968 as a major target in disease: Functional dissection and remaining challenges
- Author
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Uwe Maskos, Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems (NISC), Sorbonne Université (SU)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), he author has received funding to carry out the work of his laboratory described in the Review article, as indicated in the published papers. No funding has been received that is directly relevant to this Review article. The author has no conflict of interest to declare., and Institut Pasteur [Paris] (IP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,human genetics ,Single-nucleotide polymorphism ,Locus (genetics) ,Genome-wide association study ,Disease ,Receptors, Nicotinic ,Biology ,Bioinformatics ,Polymorphism, Single Nucleotide ,Biochemistry ,nicotine addiction ,drug discovery ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,[SCCO]Cognitive science ,0302 clinical medicine ,single nucleotide polymorphism ,Animals ,Humans ,nicotinic acetylcholine receptor ,Genetic association ,[SCCO.NEUR]Cognitive science/Neuroscience ,Human genetics ,3. Good health ,schizophrenia ,Nicotinic acetylcholine receptor ,030104 developmental biology ,Nicotinic agonist ,positive allosteric modulator ,Genome-wide Association Studies ,030217 neurology & neurosurgery - Abstract
International audience; Nicotinic acetylcholine receptors (nAChRs) are major signalling molecules in the central and peripheral nervous system. Over the last decade, they have been linked to a number of major human psychiatric and neurological conditions, like smoking, schizophrenia, Alzheimer's disease and many others. Human Genome-Wide Association Studies (GWAS) have robustly identified genetic alterations at a locus of chromosome 15q to several of these diseases. In this review, we discuss a major coding polymorphism in the alpha5 subunit, referred to as α5SNP, and its functional dissection in vitro and in vivo. Its presence at high frequency in many human populations lends itself to pharmaceutical intervention in the context of 'positive allosteric modulators' (PAMs). We will present the prospects of this novel treatment, and the remaining challenges to identify suitable molecules.
- Published
- 2020