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dc.contributor.authorShioda, Norifumien
dc.contributor.authorYabuki, Yasushien
dc.contributor.authorYamaguchi, Kouyaen
dc.contributor.authorOnozato, Misakien
dc.contributor.authorLi, Yueen
dc.contributor.authorKurosawa, Kenjien
dc.contributor.authorTanabe, Hideyukien
dc.contributor.authorOkamoto, Nobuhikoen
dc.contributor.authorEra, Takumien
dc.contributor.authorSugiyama, Hiroshien
dc.contributor.authorWada, Takahitoen
dc.contributor.authorFukunaga, Kohjien
dc.contributor.alternative塩田, 倫史ja
dc.contributor.alternative矢吹, 悌ja
dc.contributor.alternative山口, 航矢ja
dc.contributor.alternative小野里, 美咲ja
dc.contributor.alternative李, 岳ja
dc.contributor.alternative黒澤, 健司ja
dc.contributor.alternative田辺, 秀之ja
dc.contributor.alternative岡本, 伸彦ja
dc.contributor.alternative江良, 択実ja
dc.contributor.alternative杉山, 弘ja
dc.contributor.alternative和田, 敬仁ja
dc.contributor.alternative福永, 浩司ja
dc.date.accessioned2018-06-27T05:35:45Z-
dc.date.available2018-06-27T05:35:45Z-
dc.date.issued2018-05-21-
dc.identifier.issn1078-8956-
dc.identifier.urihttp://hdl.handle.net/2433/232509-
dc.description難治性疾患「ATR-X症候群」の治療に新たな光 --重度知的障がいに対する新しい治療薬候補の発見--. 京都大学プレスリリース. 2018-05-22.ja
dc.description.abstractAlpha-thalassemia X-linked intellectual disability (ATR-X) syndrome is caused by mutations in ATRX, which encodes a chromatin-remodeling protein. Genome-wide analyses in mouse and human cells indicate that ATRX tends to bind to G-rich sequences with a high potential to form G-quadruplexes. Here, we report that Atrx mutation induces aberrant upregulation of Xlr3b expression in the mouse brain, an outcome associated with neuronal pathogenesis displayed by ATR-X model mice. We show that ATRX normally binds to G-quadruplexes in CpG islands of the imprinted Xlr3b gene, regulating its expression by recruiting DNA methyltransferases. Xlr3b binds to dendritic mRNAs, and its overexpression inhibits dendritic transport of the mRNA encoding CaMKII-α, promoting synaptic dysfunction. Notably, treatment with 5-ALA, which is converted into G-quadruplex-binding metabolites, reduces RNA polymerase II recruitment and represses Xlr3b transcription in ATR-X model mice. 5-ALA treatment also rescues decreased synaptic plasticity and cognitive deficits seen in ATR-X model mice. Our findings suggest a potential therapeutic strategy to target G-quadruplexes and decrease cognitive impairment associated with ATR-X syndrome.en
dc.format.mimetypeapplication/pdf-
dc.language.isoeng-
dc.publisherSpringer Natureen
dc.rightsThis is the accepted manuscript of the article, which has been published in final form at https://doi.org/10.1038/s41591-018-0018-6en
dc.rightsThe full-text file will be made open to the public on 21 November 2018 in accordance with publisher's 'Terms and Conditions for Self-Archiving'en
dc.rightsThis is not the published version. Please cite only the published version.en
dc.rightsこの論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。ja
dc.titleTargeting G-quadruplex DNA as cognitive function therapy for ATR-X syndromeen
dc.typejournal article-
dc.type.niitypeJournal Article-
dc.identifier.jtitleNature Medicineen
dc.identifier.volume24-
dc.identifier.issue6-
dc.identifier.spage802-
dc.identifier.epage813-
dc.relation.doi10.1038/s41591-018-0018-6-
dc.textversionauthor-
dc.identifier.pmid29785027-
dc.relation.urlhttps://www.kyoto-u.ac.jp/ja/research-news/2018-05-22-
dcterms.accessRightsopen access-
datacite.date.available2018-11-21-
datacite.awardNumber16K08265-
datacite.awardNumber25110705-
jpcoar.funderName日本学術振興会ja
jpcoar.funderName日本学術振興会ja
jpcoar.funderName.alternativeJapan Society for the Promotion of Science (JSPS)en
jpcoar.funderName.alternativeJapan Society for the Promotion of Science (JSPS)en
出現コレクション:学術雑誌掲載論文等

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