GABAA 受体：结构、功能、药理学和相关疾病,Journal of Genetic Engineering and Biotechnology

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GABAA 受体：结构、功能、药理学和相关疾病
Journal of Genetic Engineering and Biotechnology ( IF 3.6 ) Pub Date : 2021-08-21 , DOI: 10.1186/s43141-021-00224-0
Amr Ghit _{1,

2} , Dina Assal ₃ , Ahmed S Al-Shami _{2,

4} , Diaa Eldin E Hussein ₅

Affiliation

γ-氨基丁酸亚型 A 受体 (GABAAR) 是 CNS 中最突出的抑制性神经递质受体。它们是具有重要生理和治疗意义的配体门控离子通道家族。GABAAR 是由 19 个亚基组成的异五聚体：6 个 α (alpha1-6)、3 个 β (beta1-3)、3 个 γ (gamma1-3)、3 个 ρ (rho1-3) 和 1 个 δ ( delta)、ε (epsilon)、π (pi) 和 θ (theta)，它们导致产生大量受体同工型。每种异构体都表现出不同的药理和生理特性。然而，大多数GABAARs由两个α亚基、两个β亚基和一个γ亚基组成，围绕中心逆时针排列为γ2β2α1β2α1。成熟受体有一个中央氯离子通道，由 GABA 神经递质门控并受多种不同药物的调节。GABA 合成或释放的变化可能对正常的大脑功能产生重大影响。此外，药物引起的分子相互作用和药理作用极为复杂。这是由于受体的结构异质性，以及存在多个变构结合位点以及可以与它们结合的多种配体。值得注意的是，GABA 能系统的功能障碍会导致多种疾病的发展。因此，了解 GABAA 受体缺陷与中枢神经系统疾病之间的关系对疾病发病机制的发现和药物开发具有重大影响。迄今为止，很少有评论详细讨论 GABAA 受体。

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GABAA receptors: structure, function, pharmacology, and related disorders

γ-Aminobutyric acid sub-type A receptors (GABAARs) are the most prominent inhibitory neurotransmitter receptors in the CNS. They are a family of ligand-gated ion channel with significant physiological and therapeutic implications. GABAARs are heteropentamers formed from a selection of 19 subunits: six α (alpha1-6), three β (beta1-3), three γ (gamma1-3), three ρ (rho1-3), and one each of the δ (delta), ε (epsilon), π (pi), and θ (theta) which result in the production of a considerable number of receptor isoforms. Each isoform exhibits distinct pharmacological and physiological properties. However, the majority of GABAARs are composed of two α subunits, two β subunits, and one γ subunit arranged as γ2β2α1β2α1 counterclockwise around the center. The mature receptor has a central chloride ion channel gated by GABA neurotransmitter and modulated by a variety of different drugs. Changes in GABA synthesis or release may have a significant effect on normal brain function. Furthermore, The molecular interactions and pharmacological effects caused by drugs are extremely complex. This is due to the structural heterogeneity of the receptors, and the existence of multiple allosteric binding sites as well as a wide range of ligands that can bind to them. Notably, dysfunction of the GABAergic system contributes to the development of several diseases. Therefore, understanding the relationship between GABAA receptor deficits and CNS disorders thus has a significant impact on the discovery of disease pathogenesis and drug development. To date, few reviews have discussed GABAA receptors in detail. Accordingly, this review aims to summarize the current understanding of the structural, physiological, and pharmacological properties of GABAARs, as well as shedding light on the most common associated disorders.

更新日期：2021-08-21

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