Neuronal nicotinic acetylcholine receptors: From the genetic analysis to neurological diseases
Neuronal nicotinic acetylcholine receptors: From the genetic analysis to neurological diseases
复制标题
DOI：
10.1016/j.bcp.2008.07.012
复制
发表时间：
2008-11-15
影响因子：
5.8
通讯作者：
Bertrand, D.
中科院分区：
文献类型：
--
作者：
Steinlein, O. K.;Bertrand, D.
烟碱乙酰胆碱受体（nAChR）是配体门控通道，其在外周神经系统中介导神经肌肉接头和神经节处的快速神经传递。在中枢神经系统中广泛表达的神经元nAChR被认为有助于神经传递和神经元活性的调节。迄今为止，已经在哺乳动物基因组中鉴定了编码这些受体的11个基因，并且它们的结构在整个进化过程中是很保守的。在遗传学领域取得的进展和大量小的遗传变异，如单核苷酸多态性的鉴定提出了新的问题，这些变化的生理和药理学后果。神经元nAChR基因多态性与精神分裂症和阿尔茨海默病等神经系统疾病之间的关联表明了更好地了解这些受体从基因到功能的重要性。在这项工作中，我们对nAChR基因在理解单基因疾病如家族性癫痫，并回顾有关nAChR基因的遗传变异及其与常见疾病和复杂病因的行为特征的关系的最新知识。(C)2008年爱思唯尔公司All rights reserved.
Nicotinic acetylcholine receptors (nAChRs) are ligand-gated channels that mediate, in the peripheral nervous system, fast neurotransmission at the neuromuscular junction and in ganglia. Widely expressed in the central nervous system neuronal nAChRs are thought to contribute both to neurotransmission and modulation of neuronal activity. To date, eleven genes encoding for these receptors have been identified in the mammalian genome and their structure is well conserved throughout evolution. Progresses made in the field of genetics and the identification of a large number of small genetic variants such as single nucleotide polymorphisms raise new questions about the physiologic and pharmacologic consequences of such variations. The finding of associations between polymorphisms in the genes encoding for the neuronal nAChRs and neurological disorders such as schizophrenia and Alzheimer disease illustrate the importance of getting a better understanding of these receptors from the gene to function.In this work we present an overview over the progress that has been made in understanding the role of nAChR genes in monogenic disorders such as familial epilepsy, and review the latest knowledge about genetic variants of the nAChR genes and their relationship with common disorders and behavioural traits of complex etiology. (C) 2008 Elsevier Inc. All rights reserved.