芋螺毒素与N-甲基-D-天冬氨酸受体结合相互作用的计算机模拟分析及其在阿尔茨海默病中的潜在治疗用途
In silico analysis of binding interaction of conantokins with NMDA receptors for potential therapeutic use in Alzheimer's disease.
作者信息
Waqar Maleeha, Batool Sidra
机构信息
Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Chak Shahzad, Islamabad 45550 Pakistan.
出版信息
J Venom Anim Toxins Incl Trop Dis. 2017 Sep 20;23:42. doi: 10.1186/s40409-017-0132-9. eCollection 2017.
BACKGROUND
The N-methyl-D-aspartate (NMDA) receptors are glutamate receptors that play vital roles in central nervous system development and are involved in synaptic plasticity, which is an essential process for learning and memory. The subunit N-methyl D-aspartate receptor subtype 2B (NR2B) is the chief excitatory neurotransmitter receptor in the mammalian brain. Disturbances in the neurotransmission mediated by the NMDA receptor are caused by its overexposure to glutamate neurotransmitter and can be treated by its binding to an antagonist. Among several antagonists, conantokins from cone snails are reported to bind to NMDA receptors.
METHODS
This study was designed to analyze the binding mode of conantokins with NMDA receptors in both humans and rats. To study interactions, dockings were performed using AutoDock 4.2 and their results were further analyzed using various computational tools.
RESULTS
Detailed analyses revealed that these ligands can bind to active site residues of both receptors as reported in previous studies.
CONCLUSIONS
In light of the present results, we suggest that these conantokins can act as antagonists of those receptors and play an important role in understanding the importance of inhibition of NMDA receptors for treatment of Alzheimer's disease.
背景
N-甲基-D-天冬氨酸（NMDA）受体是谷氨酸受体，在中枢神经系统发育中起重要作用，并参与突触可塑性，而突触可塑性是学习和记忆的重要过程。N-甲基-D-天冬氨酸受体2B亚型（NR2B）亚基是哺乳动物脑中主要的兴奋性神经递质受体。NMDA受体介导的神经传递紊乱是由其过度暴露于谷氨酸神经递质引起的，可通过与拮抗剂结合来治疗。在几种拮抗剂中，据报道来自芋螺的芋螺毒素能与NMDA受体结合。
方法
本研究旨在分析芋螺毒素与人及大鼠NMDA受体的结合模式。为研究相互作用，使用AutoDock 4.2进行对接，并使用各种计算工具进一步分析其结果。
结果
详细分析表明，如先前研究报道，这些配体可与两种受体的活性位点残基结合。
结论
根据目前的结果，我们认为这些芋螺毒素可作为这些受体的拮抗剂，并在理解抑制NMDA受体对治疗阿尔茨海默病的重要性方面发挥重要作用。
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