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s41591-018-0018-6.pdf | 89.9 MB | Adobe PDF | 見る/開く | |
s41591-018-0018-6_spl.pdf | Supplementary | 12.9 MB | Adobe PDF | 見る/開く |
完全メタデータレコード
DCフィールド | 値 | 言語 |
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dc.contributor.author | Shioda, Norifumi | en |
dc.contributor.author | Yabuki, Yasushi | en |
dc.contributor.author | Yamaguchi, Kouya | en |
dc.contributor.author | Onozato, Misaki | en |
dc.contributor.author | Li, Yue | en |
dc.contributor.author | Kurosawa, Kenji | en |
dc.contributor.author | Tanabe, Hideyuki | en |
dc.contributor.author | Okamoto, Nobuhiko | en |
dc.contributor.author | Era, Takumi | en |
dc.contributor.author | Sugiyama, Hiroshi | en |
dc.contributor.author | Wada, Takahito | en |
dc.contributor.author | Fukunaga, Kohji | en |
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.accessioned | 2018-06-27T05:35:45Z | - |
dc.date.available | 2018-06-27T05:35:45Z | - |
dc.date.issued | 2018-05-21 | - |
dc.identifier.issn | 1078-8956 | - |
dc.identifier.uri | http://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.abstract | Alpha-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.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Springer Nature | en |
dc.rights | This is the accepted manuscript of the article, which has been published in final form at https://doi.org/10.1038/s41591-018-0018-6 | en |
dc.rights | The 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.rights | This 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.title | Targeting G-quadruplex DNA as cognitive function therapy for ATR-X syndrome | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | Nature Medicine | en |
dc.identifier.volume | 24 | - |
dc.identifier.issue | 6 | - |
dc.identifier.spage | 802 | - |
dc.identifier.epage | 813 | - |
dc.relation.doi | 10.1038/s41591-018-0018-6 | - |
dc.textversion | author | - |
dc.identifier.pmid | 29785027 | - |
dc.relation.url | https://www.kyoto-u.ac.jp/ja/research-news/2018-05-22 | - |
dcterms.accessRights | open access | - |
datacite.date.available | 2018-11-21 | - |
datacite.awardNumber | 16K08265 | - |
datacite.awardNumber | 25110705 | - |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
jpcoar.funderName.alternative | Japan 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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