{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T22:39:03Z","timestamp":1790203143977,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2010,12,29]],"date-time":"2010-12-29T00:00:00Z","timestamp":1293580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004418","name":"Vrije Universiteit Brussel","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004418","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Malfunctioning of system x\n                    <jats:sub>c<\/jats:sub>\n                    <jats:sup>\u2013<\/jats:sup>\n                    , responsible for exchanging intracellular glutamate for extracellular cystine, can cause oxidative stress and excitotoxicity, both important phenomena in the pathogenesis of Parkinson's disease (PD). We used mice lacking xCT (xCT\n                    <jats:sup>_\/_<\/jats:sup>\n                    mice), the specific subunit of system x\n                    <jats:sub>c<\/jats:sub>\n                    \u02dc, to investigate the involvement of this antiporter in PD. Although cystine that is imported\n                    <jats:italic>via<\/jats:italic>\n                    system x\n                    <jats:sub>c<\/jats:sub>\n                    \u02dc is reduced to cysteine, the rate\u2010limiting substrate in the synthesis of glutathione, deletion of xCT did not result in decreased glutathione levels in striatum. Accordingly, no signs of increased oxidative stress could be observed in striatum or substantia nigra of xCT\n                    <jats:sup>_\/_<\/jats:sup>\n                    mice. In sharp contrast to expectations, xCT\n                    <jats:sup>_\/_<\/jats:sup>\n                    mice were less susceptible to 6\u2010hydroxydopamine (6\u2010OHDA)\u2010induced neurodegeneration in the substantia nigra pars compacta compared to their age\u2010matched wild\u2010type littermates. This reduced sensitivity to a PD\u2010inducing toxin might be related to the decrease of 70% in striatal extracellular glutamate levels that was observed in mice lacking xCT. The current data point toward system x\n                    <jats:sub>c<\/jats:sub>\n                    \u02dc as a possible target for the development of new pharmacotherapies for the treatment of PD and emphasize the need to continue the search for specific ligands for system x\n                    <jats:sub>c<\/jats:sub>\n                    \u02dc.\u2014Massie, A., Schallier, A., Kim, S. W., Fernando, R., Kobayashi, S., Beck, H., De Bundel, D., Vermoesen, K., Bannai, S., Smolders, I., Conrad, M., Plesnila, N., Sato, H., Michotte, Y. Dopaminergic neurons of system x\n                    <jats:sub>c<\/jats:sub>\n                    \u201c\u2010deficient mice are highly protected against 6\u2010hydroxydopamine\u2010induced toxicity.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    25, 1359\u20131369 (2011).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\\\\www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.10-177212","type":"journal-article","created":{"date-parts":[[2010,12,30]],"date-time":"2010-12-30T05:11:23Z","timestamp":1293685883000},"page":"1359-1369","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":115,"title":["Dopaminergic neurons of system x\n                    <sub>c<\/sub>\n                    <sup>\u2013<\/sup>\n                    \u2010deficient mice are highly protected against 6\u2010hydroxydopamine\u2010induced toxicity"],"prefix":"10.1096","volume":"25","author":[{"given":"Ann","family":"Massie","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry and Drug Analysis Research Group Experimental Pharmacology, Vrije Universiteit Brussel  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneleen","family":"Schallier","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry and Drug Analysis Research Group Experimental Pharmacology, Vrije Universiteit Brussel  Brussels Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Woong","family":"Kim","sequence":"additional","affiliation":[{"name":"Royal College of Surgeons in Ireland  Dublin Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruani","family":"Fernando","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics Karolinska 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