{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSLC1A2 (also known as EAAT2 or GLT‐1) is the principal high‐affinity, Na⁺‐dependent glutamate transporter predominantly expressed in astrocytes that mediates the rapid clearance of extracellular glutamate from synaptic and extrasynaptic regions. This function is critical to maintaining glutamatergic homeostasis and preventing excitotoxic neuronal injury. Studies in human brain microvessels and cortical biopsies have identified SLC1A2 as one of the major solute carrier proteins, while its strong contribution to up to 90% of total glutamate uptake has been confirmed in both physiological and pathological contexts—including neurodegenerative and demyelinating conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRegulation of SLC1A2 occurs at multiple levels. Transcriptional events—mediated by signaling pathways such as those involving NF‐κB, epidermal growth factor, and modulators like β‐lactam antibiotics (e.g., ceftriaxone)—can enhance its expression, whereas inflammatory mediators (for example, TNFα) and viral proteins (such as HIV‐1 gp120) may downregulate its transcription or promote its endocytosis. In addition, genetic studies have identified de novo mutations in SLC1A2 that cause epileptic encephalopathies, underscoring its importance in maintaining neuronal excitability."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its fundamental role in glutamate clearance, the structural organization and post‐transcriptional modulation of SLC1A2 have profound implications for its activity. Evidence indicates that SLC1A2 assembles as a trimer and undergoes alternative splicing events—giving rise to variants such as EAAT2b—that may differentially contribute to synaptic as well as extrasynaptic glutamate uptake. Abnormal expression or dysfunction of SLC1A2 is implicated in multiple neurological and psychiatric disorders including amyotrophic lateral sclerosis, schizophrenia, and alterations in presynaptic glutamate dynamics. Moreover, emerging data highlight its involvement in non‐classical settings such as in retinal photoreceptors and even in the regulation of behaviors like smoking."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "21", "end_ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nModulation of SLC1A2 function has attracted considerable therapeutic interest. Pharmacological agents such as riluzole have been shown to enhance its expression via stress‐response pathways (e.g., HSF1 activation), and gene fusion events—in cancers like gastric carcinoma—further underscore the functional versatility of SLC1A2 in metabolic rewiring. In addition, altered glutamate transporter ratios in peripheral tissues, such as pancreatic islets, illustrate its broader role in protecting cells from excitotoxic insults. Genetic polymorphisms and post‐translational modifications, including phosphorylation and ubiquitination mediated by regulatory proteins like PIKfyve, further fine‐tune its localization and activity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "31", "end_ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, recent investigations have extended the significance of SLC1A2 regulation to the aging brain and its epigenetic control. Altered promoter methylation and mislocalization from lipid raft microdomains—as observed in Alzheimer’s disease—coupled with developmental regulation in vulnerable regions such as the periventricular white matter, suggest that precise control of SLC1A2 expression is vital for both cognitive preservation and the prevention of excitotoxic injury. These studies, along with evidence of glutamatergic dysregulation in mood disorders, underscore that maintaining SLC1A2 functionality is pivotal to cell survival under both physiological aging and disease conditions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "39", "end_ref": "43"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ramzi Shawahna, Yasuo Uchida, Xavier Declèves, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptomic and quantitative proteomic analysis of transporters and drug metabolizing enzymes in freshly isolated human brain microvessels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Pharm (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/mp200129p"}], "href": "https://doi.org/10.1021/mp200129p"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21707071"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21707071"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Keetae Kim, Seok-Geun Lee, Timothy P Kegelman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of excitatory amino acid transporter-2 (EAAT2) and glutamate in neurodegeneration: opportunities for developing novel therapeutics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.22609"}], "href": "https://doi.org/10.1002/jcp.22609"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21792905"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21792905"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shannon R Hinson, Shanu F Roemer, Claudia F Lucchinetti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20081241"}], "href": "https://doi.org/10.1084/jem.20081241"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18838545"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18838545"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Seok-Geun Lee, Zhao-Zhong Su, Luni Emdad, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mechanism of ceftriaxone induction of excitatory amino acid transporter-2 expression and glutamate uptake in primary human astrocytes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M707697200"}], "href": "https://doi.org/10.1074/jbc.M707697200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18326497"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18326497"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Edward Pajarillo, Asha Rizor, Jayden Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of astrocytic glutamate transporters GLT-1 and GLAST in neurological disorders: Potential targets for neurotherapeutics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropharmacology (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuropharm.2019.03.002"}], "href": "https://doi.org/10.1016/j.neuropharm.2019.03.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30851309"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30851309"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Unknown Authors "}, {"type": "b", "children": [{"type": "t", "text": "De Novo Mutations in SLC1A2 and CACNA1A Are Important Causes of Epileptic Encephalopathies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2016.06.003"}], "href": "https://doi.org/10.1016/j.ajhg.2016.06.003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27476654"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27476654"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Raquel Sitcheran, Pankaj Gupta, Paul B Fisher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Positive and negative regulation of EAAT2 by NF-kappaB: a role for N-myc in TNFalpha-controlled repression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7600555"}], "href": "https://doi.org/10.1038/sj.emboj.7600555"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15660126"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15660126"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Zhuying Wang, Olga Pekarskaya, Meryem Bencheikh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduced expression of glutamate transporter EAAT2 and impaired glutamate transport in human primary astrocytes exposed to HIV-1 or gp120."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Virology (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0042-6822(03)00181-8"}], "href": "https://doi.org/10.1016/s0042-6822(03"}, {"type": "t", "text": "00181-8) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12890621"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12890621"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Zao-zhong Su, Magdalena Leszczyniecka, Dong-chul Kang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Insights into glutamate transport regulation in human astrocytes: cloning of the promoter for excitatory amino acid transporter 2 (EAAT2)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0136555100"}], "href": "https://doi.org/10.1073/pnas.0136555100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12578975"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12578975"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Heather A Scott, Florian M Gebhardt, Ann D Mitrovic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glutamate transporter variants reduce glutamate uptake in Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Aging (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neurobiolaging.2010.03.008"}], "href": "https://doi.org/10.1016/j.neurobiolaging.2010.03.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20416976"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20416976"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Bruna De Felice, Marco Guida, Maurizio Guida, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A miRNA signature in leukocytes from sporadic amyotrophic lateral sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2012.07.058"}], "href": "https://doi.org/10.1016/j.gene.2012.07.058"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22903028"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22903028"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Nicholas J Maragakis, Margaret Dykes-Hoberg, Jeffrey D Rothstein "}, {"type": "b", "children": [{"type": "t", "text": "Altered expression of the glutamate transporter EAAT2b in neurological disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.20003"}], "href": "https://doi.org/10.1002/ana.20003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15048885"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15048885"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Ainara Vallejo-Illarramendi, María Domercq, Fernando Pérez-Cerdá, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased expression and function of glutamate transporters in multiple sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Dis (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nbd.2005.06.017"}], "href": "https://doi.org/10.1016/j.nbd.2005.06.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16061389"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16061389"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "William Boston-Howes, Stuart L Gibb, Eric O Williams, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Caspase-3 cleaves and inactivates the glutamate transporter EAAT2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M600653200"}], "href": "https://doi.org/10.1074/jbc.M600653200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16567804"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16567804"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Jacqueline M Vink, August B Smit, Eco J C de Geus, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study of smoking initiation and current smoking."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2009.02.001"}], "href": "https://doi.org/10.1016/j.ajhg.2009.02.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19268276"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19268276"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Carlos Matute, Marcello Melone, Ainara Vallejo-Illarramendi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased expression of the astrocytic glutamate transporter GLT-1 in the prefrontal cortex of schizophrenics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glia (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/glia.20119"}], "href": "https://doi.org/10.1002/glia.20119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15494981"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15494981"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Sandra Gendreau, Stephan Voswinkel, Delany Torres-Salazar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A trimeric quaternary structure is conserved in bacterial and human glutamate transporters."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M408038200"}], "href": "https://doi.org/10.1074/jbc.M408038200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15265858"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15265858"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Hae Kyung Lee, Susan Finniss, Simona Cazacu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mesenchymal stem cells deliver exogenous miRNAs to neural cells and induce their differentiation and glutamate transporter expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stem Cells Dev (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/scd.2014.0146"}], "href": "https://doi.org/10.1089/scd.2014.0146"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25036385"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25036385"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Sandra Thier, Delia Lorenz, Michael Nothnagel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms in the glial glutamate transporter SLC1A2 are associated with essential tremor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/WNL.0b013e31825fdeed"}], "href": "https://doi.org/10.1212/WNL.0b013e31825fdeed"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22764253"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22764253"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Theresa S Rimmele, Paul A Rosenberg "}, {"type": "b", "children": [{"type": "t", "text": "GLT-1: The elusive presynaptic glutamate transporter."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurochem Int (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuint.2016.04.010"}], "href": "https://doi.org/10.1016/j.neuint.2016.04.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27129805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27129805"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Seok-Geun Lee, Keetae Kim, Timothy P Kegelman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oncogene AEG-1 promotes glioma-induced neurodegeneration by increasing glutamate excitotoxicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-11-0782"}], "href": "https://doi.org/10.1158/0008-5472.CAN-11-0782"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21852380"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21852380"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "T L Lauriat, L A McInnes "}, {"type": "b", "children": [{"type": "t", "text": "EAAT2 regulation and splicing: relevance to psychiatric and neurological disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.mp.4002065"}], "href": "https://doi.org/10.1038/sj.mp.4002065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17684493"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17684493"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Thomas Rauen, Michael Wiessner, Robert Sullivan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A new GLT1 splice variant: cloning and immunolocalization of GLT1c in the mammalian retina and brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurochem Int (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neuint.2004.04.006"}], "href": "https://doi.org/10.1016/j.neuint.2004.04.006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15337309"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15337309"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Noemí García-Tardón, Inmaculada M González-González, Jaime Martínez-Villarreal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein kinase C (PKC)-promoted endocytosis of glutamate transporter GLT-1 requires ubiquitin ligase Nedd4-2-dependent ubiquitination but not phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.355909"}], "href": "https://doi.org/10.1074/jbc.M112.355909"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22505712"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22505712"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Michelle J Chandley, Katalin Szebeni, Attila Szebeni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene expression deficits in pontine locus coeruleus astrocytes in men with major depressive disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Psychiatry Neurosci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1503/jpn.120110"}], "href": "https://doi.org/10.1503/jpn.120110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23415275"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23415275"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Qiongman Kong, Kou Takahashi, Delanie Schulte, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased glial glutamate transporter EAAT2 expression reduces epileptogenic processes following pilocarpine-induced status epilepticus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Dis (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nbd.2012.03.032"}], "href": "https://doi.org/10.1016/j.nbd.2012.03.032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22513140"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22513140"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Eiji Kobayashi, Masako Nakano, Kenta Kubota, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activated forms of astrocytes with higher GLT-1 expression are associated with cognitive normal subjects with Alzheimer pathology in human brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-19442-7"}], "href": "https://doi.org/10.1038/s41598-018-19442-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29374250"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29374250"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Guilian Tian, Qiongman Kong, Liching Lai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased expression of cholesterol 24S-hydroxylase results in disruption of glial glutamate transporter EAAT2 association with lipid rafts: a potential role in Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1471-4159.2010.06661.x"}], "href": "https://doi.org/10.1111/j.1471-4159.2010.06661.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20193040"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20193040"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Marina Bacci, Nicla Lorito, Luigi Ippolito, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reprogramming of Amino Acid Transporters to Support Aspartate and Glutamate Dependency Sustains Endocrine Resistance in Breast Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2019.06.010"}], "href": "https://doi.org/10.1016/j.celrep.2019.06.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31269432"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31269432"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Myriam Grunewald, David Menaker, Baruch I Kanner "}, {"type": "b", "children": [{"type": "t", "text": "Cysteine-scanning mutagenesis reveals a conformationally sensitive reentrant pore-loop in the glutamate transporter GLT-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M202248200"}], "href": "https://doi.org/10.1074/jbc.M202248200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11994293"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11994293"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Alice Y C Liu, Rohan Mathur, Newton Mei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuroprotective drug riluzole amplifies the heat shock factor 1 (HSF1)- and glutamate transporter 1 (GLT1)-dependent cytoprotective mechanisms for neuronal survival."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.158220"}], "href": "https://doi.org/10.1074/jbc.M110.158220"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21098017"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21098017"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Jiong Tao, Nian Tao Deng, Kalpana Ramnarayanan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CD44-SLC1A2 gene fusions in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Transl Med (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scitranslmed.3001423"}], "href": "https://doi.org/10.1126/scitranslmed.3001423"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21471434"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21471434"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Eliana S Di Cairano, Alberto M Davalli, Lucia Perego, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The glial glutamate transporter 1 (GLT1) is expressed by pancreatic beta-cells and prevents glutamate-induced beta-cell death."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.183517"}], "href": "https://doi.org/10.1074/jbc.M110.183517"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21335552"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21335552"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Marco Spangaro, Marta Bosia, Andrea Zanoletti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cognitive dysfunction and glutamate reuptake: effect of EAAT2 polymorphism in schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurosci Lett (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neulet.2012.06.030"}], "href": "https://doi.org/10.1016/j.neulet.2012.06.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22728822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22728822"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Eva-Maria Gehring, Agathe Zurn, Fabian Klaus, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of the glutamate transporter EAAT2 by PIKfyve."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000257428"}], "href": "https://doi.org/10.1159/000257428"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19910676"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19910676"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Neha Vartak-Sharma, Benjamin B Gelman, Chaitanya Joshi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Astrocyte elevated gene-1 is a novel modulator of HIV-1-associated neuroinflammation via regulation of nuclear factor-κB signaling and excitatory amino acid transporter-2 repression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.567644"}], "href": "https://doi.org/10.1074/jbc.M114.567644"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24855648"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24855648"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "S M O'Donovan, K Hasselfeld, D Bauer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glutamate transporter splice variant expression in an enriched pyramidal cell population in schizophrenia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transl Psychiatry (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/tp.2015.74"}], "href": "https://doi.org/10.1038/tp.2015.74"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26057049"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26057049"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Ilaria Guella, Marna B McKenzie, Daniel M Evans, et al. "}, {"type": "b", "children": [{"type": "t", "text": "De Novo Mutations in YWHAG Cause Early-Onset Epilepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2017.07.004"}], "href": "https://doi.org/10.1016/j.ajhg.2017.07.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28777935"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28777935"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Miriam Capri, Fabiola Olivieri, Catia Lanzarini, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of miR-31-5p, miR-141-3p, miR-200c-3p, and GLT1 as human liver aging markers sensitive to donor-recipient age-mismatch in transplants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging Cell (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/acel.12549"}], "href": "https://doi.org/10.1111/acel.12549"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27995756"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27995756"}]}, {"type": "r", "ref": 40, "children": [{"type": "t", "text": "A Hoshi, A Tsunoda, T Yamamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered expression of glutamate transporter-1 and water channel protein aquaporin-4 in human temporal cortex with Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropathol Appl Neurobiol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/nan.12475"}], "href": "https://doi.org/10.1111/nan.12475"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29405337"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29405337"}]}, {"type": "r", "ref": 41, "children": [{"type": "t", "text": "Jürgen Zschocke, Claudia Allritz, Jürgen Engele, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DNA methylation dependent silencing of the human glutamate transporter EAAT2 gene in glial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glia (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/glia.20497"}], "href": "https://doi.org/10.1002/glia.20497"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17311293"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17311293"}]}, {"type": "r", "ref": 42, "children": [{"type": "t", "text": "Adriana Medina, Sharon Burke, Robert C Thompson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glutamate transporters: a key piece in the glutamate puzzle of major depressive disorder."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Psychiatr Res (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jpsychires.2013.04.007"}], "href": "https://doi.org/10.1016/j.jpsychires.2013.04.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23706640"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23706640"}]}, {"type": "r", "ref": 43, "children": [{"type": "t", "text": "E Foran, L Rosenblum, A Bogush, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sumoylation of the astroglial glutamate transporter EAAT2 governs its intracellular compartmentalization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glia (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/glia.22677"}], "href": "https://doi.org/10.1002/glia.22677"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24753081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24753081"}]}]}]}