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The importance of the excitatory amino acid transporter 3 (EAAT3).
Neurochemistry international ( IF 4.4 ) Pub Date : 2016-05-29 , DOI: 10.1016/j.neuint.2016.05.007
Walden E Bjørn-Yoshimoto 1 , Suzanne M Underhill 2
Affiliation  

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.

中文翻译:

兴奋性氨基酸转运蛋白3(EAAT3)的重要性。

尽管神经元兴奋性氨基酸转运蛋白3(EAAT3)不一定在各处都具有相同的功能,但它在大脑中却普遍存在。这对于维持较低的谷氨酸局部浓度很重要,因为谷氨酸的主要突触后定位可以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,是表达EAAT3的神经元中谷胱甘肽(一种有效的抗氧化剂)合成的限速因子,而在GABA能神经元上,它对提供谷氨酸作为GABA合成的前体非常重要。几种疾病牵涉到EAAT3,调节这种转运蛋白可以证明是一种有用的治疗方法。EAAT3的调控可针对多个功能调控点,包括转录水平,运输和直接药理学调控,实际上,已鉴定出可在不同阶段调控EAAT3功能的化合物和实验方法,以及对EAAT3调控的观察在患者体内,我们可以深入了解这种转运蛋白的内源性功能以及功能改变的后果。这篇综述总结了为阐明EAAT3的作用和调节所做的工作。结合对患者EAAT3调节的观察,使我们深入了解了该转运蛋白的内源性功能以及功能改变的后果。这篇综述总结了为阐明EAAT3的作用和调节所做的工作。结合对患者EAAT3调节的观察,使我们深入了解了该转运蛋白的内源性功能以及功能改变的后果。这篇综述总结了为阐明EAAT3的作用和调节所做的工作。
更新日期:2016-05-24
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