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单胺转运体基因结构及其多态性与精神疾病和其他复杂疾病的关系。

Monoamine transporter gene structure and polymorphisms in relation to psychiatric and other complex disorders.

作者信息

Hahn M K, Blakely R D

机构信息

Department of Pharmacology and Center for Molecular Neuroscience, Vanderbilt University, Nashville, TN 37232-6420, USA.

出版信息

Pharmacogenomics J. 2002;2(4):217-35. doi: 10.1038/sj.tpj.6500106.

Abstract

The norepinephrine, dopamine and serotonin transporters (NET, DAT and SERT, respectively), limit cellular signaling by recapturing released neurotransmitter, and serve as targets for antidepressants and drugs of abuse, emphasizing the integral role these molecules play in neurotransmission and pathology. This has compelled researchers to search for polymorphisms in monoamine (MA) transporter genes. Studies support linkage and association of MA transporter genetic variation in psychiatric and other complex disorders. Understanding the contribution of MA transporter polymorphisms to human behavior, disease susceptibility and response to pharmacotherapies will involve further progress in linkage and association that will be aided by both definition of highly selective phenotypes and utilization of a large number of polymorphic markers. The relationship of polymorphisms to alterations in transport capacity, likely a complex interaction, involving genetic background, disease state, and medication, will elucidate the means by which MA transporter genetic variability contributes to our individuality.

摘要

去甲肾上腺素、多巴胺和5-羟色胺转运体(分别为NET、DAT和SERT)通过重新摄取释放的神经递质来限制细胞信号传导,并作为抗抑郁药和滥用药物的作用靶点,这突出了这些分子在神经传递和病理过程中所起的重要作用。这促使研究人员去寻找单胺(MA)转运体基因中的多态性。研究支持MA转运体基因变异与精神疾病及其他复杂疾病之间的连锁和关联。要理解MA转运体多态性对人类行为、疾病易感性和药物治疗反应的影响,需要在连锁和关联研究方面取得进一步进展,这将借助高度选择性表型的定义和大量多态性标记的使用来实现。多态性与转运能力改变之间的关系,可能是一种复杂的相互作用,涉及遗传背景、疾病状态和药物治疗,这将阐明MA转运体基因变异性导致个体差异的方式。

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