{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T07:52:29Z","timestamp":1790409149691,"version":"4.1.0"},"reference-count":35,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"The Swiss National Science Foundation","award":["320030_160168"],"award-info":[{"award-number":["320030_160168"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Multiple Sclerosis Journal - Experimental, Translational and Clinical"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p> Poly (ADP-ribose) polymerase 1 (PARP-1) plays pivotal roles in immune and inflammatory responses. Accumulating evidence suggests PARP-1 as a promising target for immunomodulation in multiple sclerosis and natalizumab-associated progressive multifocal leukoencephalopathy. <\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p> This study explores expression of PARP-1 and downstream effectors in multiple sclerosis and during natalizumab treatment. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p> Transcriptional expressions were studied by real-time reverse transcriptase polymerase chain reaction on CD4<jats:sup>+<\/jats:sup>T\/CD8<jats:sup>+<\/jats:sup>T\/CD14<jats:sup>+<\/jats:sup>\/B cells and peripheral blood mononuclear cells from healthy volunteers, untreated and natalizumab-treated non-progressive multifocal leukoencephalopathy and progressive multifocal leukoencephalopathy multiple sclerosis patients. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> PARP-1 expression was higher in CD4<jats:sup>+<\/jats:sup>T, CD8<jats:sup>+<\/jats:sup>T and B cells from untreated patients compared to healthy volunteers. Natalizumab treatment restored deregulated PARP-1 expression in T cells but not in B cells. Sustained upregulation of PARP-1 was associated with decreased expression of downstream PARP-1 factors such as TGFBR1\/TGFBR2\/BCL6 in B cells. Notably, a higher expression of PARP-1 was detected in progressive multifocal leukoencephalopathy patients. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p> Given the importance of PARP-1 in inflammatory processes, its upregulation in multiple sclerosis lymphocyte populations suggests a potential role in the immune pathogenesis of multiple sclerosis. Strikingly higher PARP-1 expression in progressive multifocal leukoencephalopathy cases suggests its involvement in progressive multifocal leukoencephalopathy disease pathomechanisms. These results further support the value of PARP-1 inhibitors as a potential novel therapeutic strategy for multiple sclerosis and natalizumab-associated progressive multifocal leukoencephalopathy. <\/jats:p><\/jats:sec>","DOI":"10.1177\/2055217319894604","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T11:55:57Z","timestamp":1576497357000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["PARP-1 deregulation in multiple sclerosis"],"prefix":"10.1177","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8695-1226","authenticated-orcid":false,"given":"Maria","family":"Meira","sequence":"first","affiliation":[{"name":"Departments of Biomedicine and Neurology, University Hospital Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Sievers","sequence":"additional","affiliation":[{"name":"Departments of 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