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Gotti C, Clementi FNeuronal nicotinic receptors: from structure to pathology. Prog Neurobiol 74:363-396

CNR, Institute of Neuroscience, Cellular and Molecular Pharmacology Section, Department of Medical Pharmacology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy.
Progress in Neurobiology (Impact Factor: 9.99). 01/2005; 74(6):363-96. DOI: 10.1016/j.pneurobio.2004.09.006
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ABSTRACT

Neuronal nicotinic receptors (NAChRs) form a heterogeneous family of ion channels that are differently expressed in many regions of the central nervous system (CNS) and peripheral nervous system. These different receptor subtypes, which have characteristic pharmacological and biophysical properties, have a pentameric structure consisting of the homomeric or heteromeric combination of 12 different subunits (alpha2-alpha10, beta2-beta4). By responding to the endogenous neurotransmitter acetylcholine, NAChRs contribute to a wide range of brain activities and influence a number of physiological functions. Furthermore, it is becoming evident that the perturbation of cholinergic nicotinic neurotransmission can lead to various diseases involving nAChR dysfunction during development, adulthood and ageing. In recent years, it has been discovered that NAChRs are present in a number of non-neuronal cells where they play a significant functional role and are the pathogenetic targets in several diseases. NAChRs are also the target of natural ligands and toxins including nicotine (Nic), the most widespread drug of abuse. This review will attempt to survey the major achievements reached in the study of the structure and function of NAChRs by examining their regional and cellular localisation and the molecular basis of their functional diversity mainly in pharmacological and biochemical terms. The recent availability of mice with the genetic ablation of single or double nicotinic subunits or point mutations have shed light on the role of nAChRs in major physiological functions, and we will here discuss recent data relating to their behavioural phenotypes. Finally, the role of NAChRs in disease will be considered in some details.

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    • "a Refer to supplementary data on in house verification. of these processes and lead to exaggerated/altered physiological activity (Gotti and Clementi, 2004). Although various studies with animal models of nicotine exposure exist in the literature, those examining nAChR expression are limited to prenatal, adolescent, and adult brain and only examine mRNA and receptor binding (summarized in Supplementary Tables 1 and 2). "
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    • "g . , α4β2 ; Figure 1 ; Gotti and Clementi , 2004 ; Kalamida et al . , 2007 ; Hurst et al . "
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