Kniazeff Julie
Institut de Génomique Fonctionnelle (IGF), Université de Montpellier, CNRS, INSERM, Montpellier, France.
Adv Pharmacol. 2020;88:83-113. doi: 10.1016/bs.apha.2020.02.003. Epub 2020 Mar 11.
The GABA receptor is activated by the main inhibitory neurotransmitter of the central nervous system, the γ-aminobutyric acid (GABA). The receptor is expressed in almost all neuronal and glial cells and plays a central role in the modulation of many physiological and pathological processes. The GABA receptor has been considered for years as an interesting target for the treatment of spasticity, pain, addiction, anxiety or depression. This has prompted many studies aiming at understanding the activation of the receptor and its modulation. While it belongs to the super-family of G protein-coupled receptors (GPCRs), it was rapidly evident that the GABA receptor is peculiar in the variety of allosteric modulations governing its activation. Here, I wish to gather the different aspects of the GABA receptor allosteric modulation. After presenting the main small molecule allosteric modulators known to date, the intramolecular transitions controlling the receptor activation will be summarized. In addition, recent findings obtained in the last decade on the existence of GABA receptor complexes and their influence on the receptor function will be introduced, including the GABA receptor oligomers and the auxiliary proteins associated with the receptor. These new concepts will certainly be of major interest in the future analysis of GABA receptor allosteric modulation.
γ-氨基丁酸（GABA）作为中枢神经系统的主要抑制性神经递质，可激活GABA受体。该受体几乎在所有神经元和神经胶质细胞中均有表达，在多种生理和病理过程的调节中发挥核心作用。多年来，GABA受体一直被视为治疗痉挛、疼痛、成瘾、焦虑或抑郁的一个有吸引力的靶点。这促使了许多旨在了解该受体激活及其调节机制的研究。虽然它属于G蛋白偶联受体（GPCR）超家族，但很快就发现GABA受体在控制其激活的变构调节种类方面很独特。在此，我希望汇总GABA受体变构调节的不同方面。在介绍了迄今为止已知的主要小分子变构调节剂后，将总结控制受体激活的分子内转变。此外，还将介绍过去十年中关于GABA受体复合物的存在及其对受体功能影响的最新发现，包括GABA受体寡聚体和与该受体相关的辅助蛋白。这些新概念在未来对GABA受体变构调节的分析中肯定会引起极大的兴趣。
