{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T04:45:11Z","timestamp":1784349911710,"version":"3.55.0"},"reference-count":95,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"841","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["STI2030-M"],"award-info":[{"award-number":["STI2030-M"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2022ZD0204700"],"award-info":[{"award-number":["2022ZD0204700"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31571066"],"award-info":[{"award-number":["31571066"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371357"],"award-info":[{"award-number":["82371357"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32100935"],"award-info":[{"award-number":["32100935"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2026,3,18]]},"abstract":"<jats:p>\n                    Insufficient maturation of oligodendrocyte progenitor cells (OPCs) contributes to the failure of endogenous remyelination in multiple sclerosis (MS). It remains unclear whether dysregulated oligodendroglial microRNAs (miRNAs) impede remyelination in chronic MS lesions. In this study, we demonstrated that miR-126a-3p was enriched in oligodendroglia from chronic inactive MS plaques and chronic lesions in mice with experimental autoimmune encephalomyelitis (EAE). Functional analyses revealed that miR-126a-3p inhibited OPC differentiation in vitro and that the specific deletion of miR-126a-3p in oligodendroglia accelerated the remyelination process in the EAE and lysolecithin-induced demyelination models. Mechanistically, miR-126a-3p exerted an inhibitory effect on OPC differentiation and remyelination by directly targeting peroxin-5 (\n                    <jats:italic toggle=\"yes\">Pex5<\/jats:italic>\n                    ) transcripts. A screening of a US Food and Drug Administration\u2013approved drug library based on\n                    <jats:italic toggle=\"yes\">Pex5<\/jats:italic>\n                    levels led to the identification of ganciclovir, an antiviral agent, as a potent proremyelinating agent after in vivo demyelinating events. These results identify the aberrant miR-126a-3p\u2013\n                    <jats:italic toggle=\"yes\">Pex5<\/jats:italic>\n                    axis in oligodendroglia as a potential therapeutic target to facilitate remyelination in chronic MS lesions.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adu6987","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:58:36Z","timestamp":1773856716000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Disruption of the oligodendroglial miR-126a-3p\u2013\n                    <i>Pex5<\/i>\n                    axis inhibits remyelination in chronic demyelinating lesions"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2905-809X","authenticated-orcid":true,"given":"Qi","family":"Shao","sequence":"first","affiliation":[{"name":"Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University (NMU), Shanghai 200433, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2989-6714","authenticated-orcid":true,"given":"Zhenghao","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University (NMU), Shanghai 200433, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5696-6902","authenticated-orcid":true,"given":"Weixing","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Sanatorium, Air Force Health Care Center for Special Services, Hangzhou 310000, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingyan","family":"Pu","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University (NMU), Shanghai 200433, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6583-4503","authenticated-orcid":true,"given":"Dingya","family":"Sun","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University (NMU), Shanghai 200433, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Changhai Hospital, NMU, Shanghai 200433, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Shi","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2778-9999","authenticated-orcid":true,"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University (NMU), Shanghai 200433, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3853-5548","authenticated-orcid":true,"given":"Weili","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University (NMU), Shanghai 200433, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingdong","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University (NMU), Shanghai 200433, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University (NMU), Shanghai 200433, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6038-3718","authenticated-orcid":true,"given":"Mengsheng","family":"Qiu","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 311121, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4000-1732","authenticated-orcid":true,"given":"Li","family":"Cao","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University (NMU), Shanghai 200433, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6238-4642","authenticated-orcid":true,"given":"Cheng","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Key Laboratory of Molecular Neurobiology of Ministry of Education, Naval Medical University (NMU), Shanghai 200433, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aba6905"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11314"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041359"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2016.02.004"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2480"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn080"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-061010-113629"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002106"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl217"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn096"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181a8260a"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2017.115"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11940-019-0574-1"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2172"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80515-2"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.07.018"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041358"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1667-1"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13045"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(12)70309-5"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10661"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0560-7"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200940032"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp300"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.02.018"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1317182110"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.01.027"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15618"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.152"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1303488"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202105442"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2855"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2702"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00678-5"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.11.024"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-01980-7"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0619-8"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/2051-5960-1-70"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg153"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh032"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.004895"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1631-4"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028977"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24224"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.11.005"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004836-200110000-00006"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.82.6.704"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3618"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12647"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.7326\/AITC202106150"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.26858"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn917"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4578230"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458513490542"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2012.00013"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2008.07.002"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08889"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2012.05.021"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514524998"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm807"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.01.002"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1710"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/0736-5748(86)90003-1"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng2070"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-02-00601.1998"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.1015"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24524"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-17-06404.2000"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/121.12.2221"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa010994"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.14236"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14335"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI183941"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)32346-2"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-025-02212-x"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120696"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.11.032"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1393842"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.05.013"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1510-18.2018"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0162858"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0010-22.2022"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adn9980"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2468-14.2015"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201643668"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2010.1597"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-12-64"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-017-0153-y"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.1600"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2021.577777"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3109"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-021-00696-7"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-018-0207-9"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22578"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2019.105088"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adu6987","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:58:49Z","timestamp":1773856729000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adu6987"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":95,"journal-issue":{"issue":"841","published-print":{"date-parts":[[2026,3,18]]}},"alternative-id":["10.1126\/scitranslmed.adu6987"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adu6987","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]},"assertion":[{"value":"2024-11-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-04","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadu6987"}}