Bjørn-Yoshimoto Walden E, Underhill Suzanne M
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 København Ø, Denmark.
National Institute of Mental Health, National Institutes of Health, 35 Convent Drive Room 3A: 210 MSC3742, Bethesda, MD 20892-3742, USA.
Neurochem Int. 2016 Sep;98:4-18. doi: 10.1016/j.neuint.2016.05.007. Epub 2016 May 24.
The neuronal excitatory amino acid transporter 3 (EAAT3) is fairly ubiquitously expressed in the brain, though it does not necessarily maintain the same function everywhere. It is important in maintaining low local concentrations of glutamate, where its predominant post-synaptic localization can buffer nearby glutamate receptors and modulate excitatory neurotransmission and synaptic plasticity. It is also the main neuronal cysteine uptake system acting as the rate-limiting factor for the synthesis of glutathione, a potent antioxidant, in EAAT3 expressing neurons, while on GABAergic neurons, it is important in supplying glutamate as a precursor for GABA synthesis. Several diseases implicate EAAT3, and modulation of this transporter could prove a useful therapeutic approach. Regulation of EAAT3 could be targeted at several points for functional modulation, including the level of transcription, trafficking and direct pharmacological modulation, and indeed, compounds and experimental treatments have been identified that regulate EAAT3 function at different stages, which together with observations of EAAT3 regulation in patients is giving us insight into the endogenous function of this transporter, as well as the consequences of altered function. This review summarizes work done on elucidating the role and regulation of EAAT3.
神经元兴奋性氨基酸转运体3（EAAT3）在大脑中广泛表达，但其功能在各处不一定相同。它在维持局部低浓度谷氨酸方面很重要，其主要的突触后定位可缓冲附近的谷氨酸受体，并调节兴奋性神经传递和突触可塑性。它也是主要的神经元半胱氨酸摄取系统，在表达EAAT3的神经元中作为合成强效抗氧化剂谷胱甘肽的限速因子，而在γ-氨基丁酸能神经元中，它在提供谷氨酸作为γ-氨基丁酸合成的前体方面很重要。几种疾病与EAAT3有关，调节这种转运体可能是一种有用的治疗方法。对EAAT3的调节可针对几个功能调节点，包括转录水平、转运和直接药理调节，事实上，已经鉴定出在不同阶段调节EAAT3功能的化合物和实验性治疗方法，这些与患者中EAAT3调节的观察结果一起，让我们深入了解这种转运体的内源性功能以及功能改变的后果。本综述总结了在阐明EAAT3的作用和调节方面所做的工作。
