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G protein-coupled receptor heteromers are key players in substance use disorder.
Neuroscience & Biobehavioral Reviews ( IF 8.2 ) Pub Date : 2018-09-29 , DOI: 10.1016/j.neubiorev.2018.09.026
Lyes Derouiche 1 , Dominique Massotte 1
Affiliation  

G protein-coupled receptors (GPCR) represent the largest family of membrane proteins in the human genome. Physical association between two different GPCRs is linked to functional interactions which generates a novel entity, called heteromer, with specific ligand binding and signaling properties. Heteromerization is increasingly recognized to take place in the mesocorticolimbic pathway and to contribute to various aspects related to substance use disorder. This review focuses on heteromers identified in brain areas relevant to drug addiction. We report changes at the molecular and cellular levels that establish specific functional impact and highlight behavioral outcome in preclinical models. Finally, we briefly discuss selective targeting of native heteromers as an innovative therapeutic option.

中文翻译:

G蛋白偶联受体异聚体是物质使用障碍的关键因素。

G蛋白偶联受体(GPCR)代表了人类基因组中最大的膜蛋白家族。两种不同GPCR之间的物理关联与功能性相互作用相关联,该功能性相互作用产生了一种新的实体,称为异源单体,具有特定的配体结合和信号传导特性。越来越多地认识到异构化发生在中皮层皮质途径中,并有助于与药物滥用相关的各个方面。这篇综述着重于在与药物成瘾有关的大脑区域中发现的异聚体。我们报告了在分子和细胞水平上的变化,这些变化建立了特定的功能影响并突出了临床前模型中的行为结果。最后,我们简要讨论了将天然异聚体选择性靶向作为一种创新的治疗选择。
更新日期:2018-09-29
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