{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:16:45Z","timestamp":1791213405757,"version":"4.1.0"},"reference-count":155,"publisher":"IMR Press","issue":"3","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Biosci. (Landmark Ed)"],"abstract":"<jats:p>Glial cells play an essential role in the complex function of the nervous system. In particular, astrocytes provide nutritive support for neuronal cells and are involved in regulating synaptic transmission. Oligodendrocytes ensheath axons and support information transfer over long distances. Microglial cells constitute part of the innate immune system in the brain. Glial cells are equipped with the glutamate-cystine-exchanger xCT (SLC7A11), the catalytic subunit of system xc-, and the excitatory amino acid transporter 1 (EAAT1, GLAST) and EAAT2 (GLT-1). Thereby, glial cells maintain balanced extracellular glutamate levels that enable synaptic transmission and prevent excitotoxic states. Expression levels of these transporters, however, are not fixed. Instead, expression of glial glutamate transporters are highly regulated in reaction to the external situations. Interestingly, such regulation and homeostasis is lost in diseases such as glioma, (tumor-associated) epilepsy, Alzheimer\u2019s disease, Parkinson\u2019s disease, amyotrophic lateral sclerosis or multiple sclerosis. Upregulation of system xc- (xCT or SLC7A11) increases glutamate export from the cell, while a downregulation of EAATs decreases intracellular glutamate import. Occurring simultaneously, these reactions entail excitotoxicity and thus harm neuronal function. The release of glutamate via the antiporter system xc- is accompanied by the import of cystine\u2014an amino acid essential in the antioxidant glutathione. This homeostasis between excitotoxicity and intracellular antioxidant response is plastic and off-balance in central nervous system (CNS) diseases. System xc- is highly expressed on glioma cells and sensitizes them to ferroptotic cell death. Hence, system xc- is a potential target for chemotherapeutic add-on therapy. Recent research reveals a pivotal role of system xc- and EAAT1\/2 in tumor-associated and other types of epilepsy. Numerous studies show that in Alzheimer\u2019s disease, amyotrophic lateral sclerosis and Parkinson\u2019s disease, these glutamate transporters are dysregulated\u2014and disease mechanisms could be interposed by targeting system xc- and EAAT1\/2. Interestingly, in neuroinflammatory diseases such as multiple sclerosis, there is growing evidence for glutamate transporter involvement. Here, we propose that the current knowledge strongly suggest a benefit from rebalancing glial transporters during treatment.<\/jats:p>","DOI":"10.31083\/j.fbl2803057","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T03:07:45Z","timestamp":1679281665000},"source":"Crossref","is-referenced-by-count":58,"title":["Glial Glutamate Transporter-Mediated Plasticity: System xc-\/xCT\/SLC7A11 and EAAT1\/2 in Brain Diseases"],"prefix":"10.31083","volume":"28","author":[{"given":"Marc","family":"Dahlmanns","sequence":"first","affiliation":[{"name":"Institute for Physiology and Pathophysiology, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana Katharina","family":"Dahlmanns","sequence":"first","affiliation":[{"name":"Institute for Physiology and Pathophysiology, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolai","family":"Savaskan","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), 91054 Erlangen, Germany"},{"name":"Department of Public Health Neuk\u00f6lln, District Office Neuk\u00f6lln of Berlin Neuk\u00f6lln, 12359 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Herbert","family":"Steiner","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Paracelsus Medical University, 90471 Nuremberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard","family":"Yakubov","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg (FAU), 91054 Erlangen, Germany"},{"name":"Department of Neurosurgery, Paracelsus Medical University, 90471 Nuremberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Perea G, Navarrete M, Araque A. 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