{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:48:06Z","timestamp":1782978486646,"version":"3.54.5"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,6,9]],"date-time":"2024-06-09T00:00:00Z","timestamp":1717891200000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971013 and 82271221"],"award-info":[{"award-number":["81971013 and 82271221"]}],"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":["82101336"],"award-info":[{"award-number":["82101336"]}],"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":["81870915 and 82071197"],"award-info":[{"award-number":["81870915 and 82071197"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>White matter hyperintensities\u00a0(WMHs) refer to a group of diseases with numerous etiologies while oligodendrocytes remain the centerpiece in the pathogenesis of WMHs. Ring Finger Protein 216 (RNF216) encodes a ubiquitin ligase, and its mutation begets WMHs, ataxia, and cognitive decline in patients. Yet no study has revealed the function of RNF216 in oligodendroglia and WHIs before. In this study, we summarized the phenotypes of RNF216\u2010mutation cases and explored the normal distribution of RNF216 in distinct brain regions and neuronal cells by bioinformatic analysis. Furthermore, MO3.13, a human oligodendrocyte cell line, was applied to study the function alteration after RNF216 knockdown. As a result, WMHs were the most common symptom in RNF216\u2010mutated diseases, and RNF216 was indeed relatively enriched in corpus callosum and oligodendroglia in humans. The downregulation of RNF216 in oligodendroglia remarkably hampered cell proliferation by inhibiting the Akt pathway while having no significant effect on cell injury and oligodendrocyte maturation. Combining clinical, bioinformatical, and experimental evidence, our study implied the pivotal role of RNF216 in WMHs which might serve as a potent target in the therapy of WMHs.<\/jats:p>","DOI":"10.1002\/cbf.4057","type":"journal-article","created":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T02:03:45Z","timestamp":1717985025000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ring finger protein 216 loss\u2010of\u2010function induces white matter hyperintensities by inhibiting oligodendroglia proliferation"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-4979-6491","authenticated-orcid":false,"given":"Wenqing","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Neurology, Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keliang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Dong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Neurology, Huashan Hospital Fudan University Shanghai China"},{"name":"National Center for Neurological Disorders, Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6449-8106","authenticated-orcid":false,"given":"Mei","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Neurology, Huashan Hospital Fudan University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.10"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.175"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0851-x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2015.00340"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx338"},{"issue":"9","key":"e_1_2_9_7_1","first-page":"1466","article-title":"New syndrome characterized by hypomyelination with atrophy of the basal ganglia and cerebellum","volume":"23","author":"Knaap MS","year":"2002","journal-title":"AJNR Am J Neuroradiol"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-06401-x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.21016"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/neurolint14010002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001002"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2021.764486"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1066"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-020-0779-1"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000112"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M108675200"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.4161\/15548627.2014.981792"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.05.016"},{"issue":"5","key":"e_1_2_9_19_1","first-page":"430","article-title":"Clinical and genetic spectrum of RNF216\u2010related disorder: a new case and literature review","volume":"61","author":"Wu C","year":"2024","journal-title":"J Med Genet"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12551"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2022.104386"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8091096"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215993"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1136\/practneurol-2017-001674"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.4081\/ni.2016.6444"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.12721"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.07.012"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.09.014"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-023-01529-4"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-021-01953-0"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx045"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22451"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2023-256994"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001521"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.12839"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51047"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2017.5121"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4598"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-021-00855-5"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.00626"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2021.641397"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1739-1"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2024.103347"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20160380"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-020-01136-4"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-017-0580-x"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awt326"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-104064"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2021.04.006"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-018-0081-4"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00917-2"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-015-9609-x"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.21841"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.20984"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23127"}],"container-title":["Cell Biochemistry and Function"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbf.4057","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T04:18:08Z","timestamp":1760329088000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/cbf.4057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6]]},"references-count":54,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/cbf.4057"],"URL":"https:\/\/doi.org\/10.1002\/cbf.4057","archive":["Portico"],"relation":{},"ISSN":["0263-6484","1099-0844"],"issn-type":[{"value":"0263-6484","type":"print"},{"value":"1099-0844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6]]},"assertion":[{"value":"2023-09-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e4057"}}