谷氨酸的结构类似物 L-茶氨酸对 GluR5 Kainate 受体的抑制作用及其在抗兴奋性毒性方面的应用前景

Satarupa Deb, Anupom Borah
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引用次数: 0

摘要

背景:对兴奋性神经递质做出反应的受体过度激活会导致各种有害结果,如无法适当调节钙水平、产生自由基、启动线粒体通透性转换,以及随后由兴奋性毒性引起的二次损伤。茶叶中的一种非蛋白质氨基酸--L-茶氨酸,在结构上与谷氨酸有关,谷氨酸是大脑中主要的刺激性神经递质。以往的报告强调了它与谷氨酸受体结合的能力:目的:深入了解离子型谷氨酸受体与 L-茶氨酸之间的结合相容性是非常必要的:在这项分子对接研究中,使用 Molegro Virtual Docker 7.0.0,评估了 L-茶氨酸的拮抗作用及其对 GluR5 kainate 受体抑制可能产生的治疗效果,并将其与我们熟悉的 AMPA 和 kainite 受体拮抗剂氰基喹喔啉(CNQX)和二硝基喹喔啉(DNQX)进行了比较:结果表明,L-茶氨酸与 GluR5 受体的结合能力高于谷氨酸,但无法超越竞争性拮抗剂 CNQX 和 DNQX 的高结合倾向。尽管如此,L-茶氨酸的药物亲和力评分和血脑屏障穿越潜力均高于 CNQX 和 DNQX:结论:本研究推断了左旋茶氨酸的优势,它可以作为一种安全有效的替代天然疗法,用于挽救兴奋性毒性导致的神经元死亡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Inhibitory Role of L-theanine, a Structural Analogue of Glutamate, against GluR5 Kainate Receptor and its Prospective Utility against Excitotoxicity.

Background: Overactivation of receptors that respond to excitatory neurotransmitters can result in various harmful outcomes, such as the inability to properly modulate calcium levels, generation of free radicals, initiation of the mitochondrial permeability transition, and subsequent secondary damage caused by excitotoxicity. A non-proteinogenic amino acid of tea, L-theanine, is structurally related to glutamate, the major stimulatory neurotransmitter in the brain. Previous reports have emphasised its ability to bind with glutamate receptors.

Objective: An in-depth understanding of the binding compatibility between ionotropic glutamate receptors and L-theanine is a compelling necessity.

Methods: In this molecular docking study, the antagonistic effect of L-theanine and its possible therapeutic benefit in GluR5 kainate receptor inhibition has been evaluated and compared to the familiar AMPA and kainite receptor antagonists, cyanoquinoxaline (CNQX) and dinitroquinoxaline (DNQX), using Molegro Virtual Docker 7.0.0.

Results: The capacity of L-theanine to cohere with the GluR5 receptor was revealed to be higher than that of glutamate, although it could not surpass the high binding tendency of competitive antagonists CNQX and DNQX. Nonetheless, the drug-likeness score and the blood-brain barrier traversing potential of L-theanine were higher than CNQX and DNQX.

Conclusion: The study provides an inference to the advantage of L-theanine, which can be a safe and effective alternative natural therapy for rescuing neuronal death due to excitotoxicity.

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