{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T23:35:47Z","timestamp":1789601747520,"version":"build-2803163510"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"16","license":[{"start":{"date-parts":[[2020,10,6]],"date-time":"2020-10-06T00:00:00Z","timestamp":1601942400000},"content-version":"vor","delay-in-days":183,"URL":"http:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/501100000272","name":"DH | National Institute for Health Research","doi-asserted-by":"publisher","award":["NS099594; AI135601"],"award-info":[{"award-number":["NS099594; AI135601"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"Chinese National Natural Science Foundation","doi-asserted-by":"crossref","award":["81771345; 31970771"],"award-info":[{"award-number":["81771345; 31970771"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,4,21]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Current immunomodulatory therapies for multiple sclerosis (MS) can effectively inhibit autoimmune response, but largely fail to promote myelin repair. This therapeutic deficiency is due mainly to the failure of treatment to promote remyelination in the central nervous system (CNS). Here we show that ursolic acid (UA), a natural triterpenoid, in addition to its well-known antiinflammatory effect, also directly stimulates oligodendrocyte maturation and CNS myelin repair. Mechanisms of UA action involve induction of pro-myelinating neurotrophic factor in astrocytes by PPAR\u03b3\/CREB signaling and regulation of myelin-related gene expression during oligodendrocyte maturation via PPAR\u03b3 activation. Our data demonstrate that UA has great potential as an agent for MS, especially at the chronic-progressive stage, because of its capacity in both immunomodulation and neural repair.<\/jats:p>","DOI":"10.1073\/pnas.2000208117","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T20:21:18Z","timestamp":1586204478000},"page":"9082-9093","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":95,"title":["A dual effect of ursolic acid to the treatment of multiple sclerosis through both immunomodulation and direct remyelination"],"prefix":"10.1073","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2463-4599","authenticated-orcid":false,"given":"Yuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107;"},{"name":"Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi\u2019an 710119, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107;"},{"name":"Key Laboratory of the Ministry of Education for Medicinal Resources and Natural Pharmaceutical Chemistry, College of Life Sciences, Shaanxi Normal University, Xi\u2019an 710119, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogoljub","family":"Ciric","sequence":"additional","affiliation":[{"name":"Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Curtis","sequence":"additional","affiliation":[{"name":"Department of Pathology, Thomas Jefferson University, Philadelphia, PA 19107;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Mucosal Immunology Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdolmohamad","family":"Rostami","sequence":"additional","affiliation":[{"name":"Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang-Xian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,4,6]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-018-0082-z"},{"key":"e_1_3_3_2_2","first-page":"527","article-title":"Progressive multiple sclerosis: From pathogenic mechanisms to treatment","volume":"140","author":"Correale J.","year":"2017","unstructured":"J. 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