{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T15:10:03Z","timestamp":1789053003199,"version":"build-2803163510"},"reference-count":79,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T00:00:00Z","timestamp":1631059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"publisher","award":["DMR-109-246"],"award-info":[{"award-number":["DMR-109-246"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"publisher","award":["NHRI-EX109-10731NI"],"award-info":[{"award-number":["NHRI-EX109-10731NI"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 108-2314-B-039-002; MOST 109-2622-B-039-001-CC2; MOST 109-2314-B-039-039-MY3"],"award-info":[{"award-number":["MOST 108-2314-B-039-002; MOST 109-2622-B-039-001-CC2; MOST 109-2314-B-039-039-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Glutamate, a crucial excitatory neurotransmitter, plays a major role in the modulation of schizophrenia\u2019s pathogenesis. New drug developments for schizophrenia have been prompted by the hypoglutamatergic hypothesis of schizophrenia. The cystine\/glutamate antiporter system xc\u2212 is related to glutamate-release regulation. Patients with schizophrenia were recently discovered to exhibit downregulation of xc\u2212 subunits\u2014the solute carrier (SLC) family 3 member 2 and the SLC family 7 member 11. We searched for relevant studies from 1980, when Bannai and Kitamura first identified the protein subunit system xc\u2212 in lung fibroblasts, with the aim of compiling the biological, functional, and pharmacological characteristics of antiporter xc\u2212, which consists of several subunits. Some of them can significantly stimulate the human brain through the glutamate pathway. Initially, extracellular cysteine activates neuronal xc\u2212, causing glutamate efflux. Next, excitatory amino acid transporters enhance the unidirectional transportation of glutamate and sodium. These two biochemical pathways are also crucial to the production of glutathione, a protective agent for neural and glial cells and astrocytes. Investigation of the expression of system xc\u2212 genes in the peripheral white blood cells of patients with schizophrenia can facilitate better understanding of the mental disorder and future development of novel biomarkers and treatments for schizophrenia. In addition, the findings further support the hypoglutamatergic hypothesis of schizophrenia.<\/jats:p>","DOI":"10.3390\/ijms22189718","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T10:12:03Z","timestamp":1631095923000},"page":"9718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Cystine\/Glutamate Antiporter in Schizophrenia: From Molecular Mechanism to Novel Biomarker and Treatment"],"prefix":"10.3390","volume":"22","author":[{"given":"Chung-Chieh","family":"Hung","sequence":"first","affiliation":[{"name":"Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Psychiatry, China Medical University Hospital, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chieh-Hsin","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2162-8174","authenticated-orcid":false,"given":"Hsien-Yuan","family":"Lane","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medical Science, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Psychiatry, China Medical University Hospital, Taichung 40402, Taiwan"},{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan"},{"name":"Department of Psychology, College of Medical and Health Sciences, Asia University, Taichung 41354, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S0264180100000904","article-title":"Schizophrenia: Manifestations, incidence and course in different cultures A World Health Organization Ten-Country Study","volume":"20","author":"Jablensky","year":"1992","journal-title":"Psychol. 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