Neuroprotective role of GLT-1/EAAT2 in glutamate-induced excitotoxicity

IF 2.3 3区心理学 Q2 BEHAVIORAL SCIENCES

Behavioural Brain Research Pub Date : 2025-09-04 DOI:10.1016/j.bbr.2025.115804

Yi Zhang, Wen Liu, Tao Huang, Lingling Liu, Xiuping Chen

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引用次数: 0

Abstract

Glutamate-mediated excitotoxicity represents a common pathomechanism in neurological disorders. As the predominant glutamate transporter in the central nervous system, glutamate transporter 1 (GLT-1, known as EAAT2 in humans) plays a crucial role in maintaining glutamate homeostasis and preventing excitotoxicity through its Na⁺-dependent transport mechanism. Key functions of GLT-1 include reducing extracellular glutamate concentration, regulating calcium homeostasis, suppressing oxidative stress, preserving mitochondrial integrity, and modulating neuroinflammatory processes by limiting microglial activation. This review systematically examines the role of GLT-1 in cerebral ischemia/reperfusion injury, neurodegenerative diseases, epilepsy, chronic pain, and psychiatric disorders. Furthermore, the therapeutic potential of GLT-1 is explored, encompassing pharmacological activators (e.g., ceftriaxone), gene therapy approaches (e.g., adeno-associated virus (AAV)-mediated GLT-1 overexpression), and non-coding RNA-based strategies. Future research should focus on elucidating the precise regulatory networks of GLT-1 and developing targeted therapies with enhanced specificity and minimal off-target effects.

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GLT-1/EAAT2在谷氨酸诱导的兴奋性毒性中的神经保护作用。

谷氨酸介导的兴奋性毒性是神经系统疾病的一种常见病理机制。谷氨酸转运蛋白1 （glutamate transporter 1, GLT-1，在人类中称为EAAT2）是中枢神经系统中主要的谷氨酸转运蛋白，它通过Na⁺依赖的转运机制在维持谷氨酸稳态和防止兴奋毒性中起着至关重要的作用。GLT-1的主要功能包括降低细胞外谷氨酸浓度，调节钙稳态，抑制氧化应激，保持线粒体完整性，并通过限制小胶质细胞激活来调节神经炎症过程。这篇综述系统地探讨了GLT-1在脑缺血/再灌注损伤、神经退行性疾病、癫痫、慢性疼痛和精神疾病中的作用。此外，研究人员还探讨了GLT-1的治疗潜力，包括药物激活剂（如头孢曲松）、基因治疗方法（如腺相关病毒（AAV）介导的GLT-1过表达）和基于非编码rna的策略。未来的研究应侧重于阐明GLT-1的精确调控网络，并开发具有更高特异性和最小脱靶效应的靶向治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Behavioural Brain Research 医学-行为科学

CiteScore

5.60

自引率

0.00%

发文量

383

审稿时长

61 days

期刊介绍： Behavioural Brain Research is an international, interdisciplinary journal dedicated to the publication of articles in the field of behavioural neuroscience, broadly defined. Contributions from the entire range of disciplines that comprise the neurosciences, behavioural sciences or cognitive sciences are appropriate, as long as the goal is to delineate the neural mechanisms underlying behaviour. Thus, studies may range from neurophysiological, neuroanatomical, neurochemical or neuropharmacological analysis of brain-behaviour relations, including the use of molecular genetic or behavioural genetic approaches, to studies that involve the use of brain imaging techniques, to neuroethological studies. Reports of original research, of major methodological advances, or of novel conceptual approaches are all encouraged. The journal will also consider critical reviews on selected topics.