caa a22 4500 606175822 CHVBK 20210128100744.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s00018-015-1937-8 doi (NATIONALLICENCE)springer-10.1007/s00018-015-1937-8 Glutamate transporter EAAT2: regulation, function, and potential as a therapeutic target for neurological and psychiatric disease [Elektronische Daten] [Kou Takahashi, Joshua Foster, Chien-Liang Lin] Glutamate is the predominant excitatory neurotransmitter in the central nervous system. Excitatory amino acid transporter 2 (EAAT2) is primarily responsible for clearance of extracellular glutamate to prevent neuronal excitotoxicity and hyperexcitability. EAAT2 plays a critical role in regulation of synaptic activity and plasticity. In addition, EAAT2 has been implicated in the pathogenesis of many central nervous system disorders. In this review, we summarize current understanding of EAAT2, including structure, pharmacology, physiology, and functions, as well as disease relevancy, such as in stroke, Parkinson's disease, epilepsy, amyotrophic lateral sclerosis, Alzheimer's disease, major depressive disorder, and addiction. A large number of studies have demonstrated that up-regulation of EAAT2 protein provides significant beneficial effects in many disease models suggesting EAAT2 activation is a promising therapeutic approach. Several EAAT2 activators have been identified. Further understanding of EAAT2 regulatory mechanisms could improve development of drug-like compounds that spatiotemporally regulate EAAT2. Springer Basel, 2015 Glutamate transporters nationallicence Astrocytes nationallicence Neurodegenerative disease nationallicence Glutamic acid nationallicence GLT-1 nationallicence Depression nationallicence Ceftriaxone nationallicence LDN/OSU-0212320 nationallicence NF-kB : Nuclear factor kappa B nationallicence Sp1 : Specificity protein 1 nationallicence NFAT : Nuclear factor of activated T-cells nationallicence YY1 : Yin Yang 1 nationallicence EGF : Epidermal growth factor nationallicence TGF-alpha : Transforming growth factor alpha nationallicence EGR : Early growth response protein nationallicence Takahashi Kou Department of Neuroscience, The Ohio State University, 333 West 10th Avenue, 43210, Columbus, OH, USA aut Foster Joshua Department of Neuroscience, The Ohio State University, 333 West 10th Avenue, 43210, Columbus, OH, USA aut Lin Chien-Liang Department of Neuroscience, The Ohio State University, 333 West 10th Avenue, 43210, Columbus, OH, USA aut Cellular and Molecular Life Sciences Springer Basel 72/18(2015-09-01), 3489-3506 1420-682X 72:18<3489 2015 72 18 https://doi.org/10.1007/s00018-015-1937-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1937-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Takahashi Kou Department of Neuroscience, The Ohio State University, 333 West 10th Avenue, 43210, Columbus, OH, USA aut NATIONALLICENCE 700 1- Foster Joshua Department of Neuroscience, The Ohio State University, 333 West 10th Avenue, 43210, Columbus, OH, USA aut NATIONALLICENCE 700 1- Lin Chien-Liang Department of Neuroscience, The Ohio State University, 333 West 10th Avenue, 43210, Columbus, OH, USA aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/18(2015-09-01), 3489-3506 1420-682X 72:18<3489 2015 72 18