{"created":"2024-10-31T00:54:53.221003+00:00","id":2019677,"links":{},"metadata":{"_buckets":{"deposit":"9c4c2901-76fa-4906-a335-474c8fc7c78a"},"_deposit":{"created_by":7,"id":"2019677","owners":[7],"pid":{"revision_id":0,"type":"depid","value":"2019677"},"status":"published"},"_oai":{"id":"oai:ocu-omu.repo.nii.ac.jp:02019677","sets":["1623632832836:1721355153493"]},"author_link":[],"item_1617186331708":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"C9orf72 Hexanucleotide Repeat Expansion-Related Neuropathology Is Attenuated by Nasal Rifampicin in Mice","subitem_title_language":"en"}]},"item_1617186419668":{"attribute_name":"作成者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNames":[{"affiliationName":"Osaka City University","affiliationNameLang":"en"}]}],"creatorNames":[{"creatorName":"Hatanaka, Yukari","creatorNameLang":"en"},{"creatorName":"ハタナカ, ユカリ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"0000-0002-7869-5741","nameIdentifierScheme":"ORCID","nameIdentifierURI":"https://orcid.org/0000-0002-7869-5741"}]},{"creatorAffiliations":[{"affiliationNames":[{"affiliationName":"Osaka City University","affiliationNameLang":"en"}]}],"creatorNames":[{"creatorName":"Umeda, Tomohiro","creatorNameLang":"en"},{"creatorName":"ウメダ, トモヒロ","creatorNameLang":"ja-Kana"},{"creatorName":"梅田, 知宙","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"1000070549790","nameIdentifierScheme":"KAKEN2","nameIdentifierURI":"https://nrid.nii.ac.jp/nrid/1000070549790"},{"nameIdentifier":"0000-0001-9915-623X","nameIdentifierScheme":"ORCID","nameIdentifierURI":"https://orcid.org/0000-0001-9915-623X"}]},{"creatorAffiliations":[{"affiliationNames":[{"affiliationName":"Osaka City University","affiliationNameLang":"en"}]}],"creatorNames":[{"creatorName":"Shigemori, Keiko","creatorNameLang":"en"},{"creatorName":"シゲモリ, ケイコ","creatorNameLang":"ja-Kana"},{"creatorName":"重森, 慶子","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"0000-0002-1877-988X","nameIdentifierScheme":"ORCID","nameIdentifierURI":"https://orcid.org/0000-0002-1877-988X"}]},{"creatorAffiliations":[{"affiliationNames":[{"affiliationName":"Kindai University","affiliationNameLang":"en"}]}],"creatorNames":[{"creatorName":"Takeuchi, Toshihide","creatorNameLang":"en"},{"creatorName":"タケウチ, トシヒデ","creatorNameLang":"ja-Kana"},{"creatorName":"竹内, 敏秀","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"1000070600120","nameIdentifierScheme":"KAKEN2","nameIdentifierURI":"https://nrid.nii.ac.jp/nrid/1000070600120"},{"nameIdentifier":"7000009408","nameIdentifierScheme":"RESEARCHMAP","nameIdentifierURI":"https://researchmap.jp/7000009408"}]},{"creatorAffiliations":[{"affiliationNames":[{"affiliationName":"Kindai University","affiliationNameLang":"en"}]}],"creatorNames":[{"creatorName":"Nagai, Yoshitaka","creatorNameLang":"en"},{"creatorName":"ナガイ, ヨシタカ","creatorNameLang":"ja-Kana"},{"creatorName":"永井, 義隆","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"1000060335354","nameIdentifierScheme":"KAKEN2","nameIdentifierURI":"https://nrid.nii.ac.jp/nrid/1000060335354"},{"nameIdentifier":"0000-0003-1037-3129","nameIdentifierScheme":"ORCID","nameIdentifierURI":"https://orcid.org/0000-0003-1037-3129"}]},{"creatorAffiliations":[{"affiliationNames":[{"affiliationName":"Osaka City University","affiliationNameLang":"en"}]}],"creatorNames":[{"creatorName":"Tomiyama, Takami","creatorNameLang":"en"},{"creatorName":"トミヤマ, タカミ","creatorNameLang":"ja-Kana"},{"creatorName":"富山, 貴美","creatorNameLang":"ja"}],"nameIdentifiers":[{"nameIdentifier":"1000010305633","nameIdentifierScheme":"KAKEN2","nameIdentifierURI":"https://nrid.nii.ac.jp/nrid/1000010305633"},{"nameIdentifier":"0000-0001-6040-0178","nameIdentifierScheme":"ORCID","nameIdentifierURI":"https://orcid.org/0000-0001-6040-0178"}]}]},"item_1617186499011":{"attribute_name":"権利情報","attribute_value_mlt":[{"subitem_rights":"クリエイティブ・コモンズ　表示 4.0 国際","subitem_rights_language":"ja","subitem_rights_resource":"https://creativecommons.org/licenses/by/4.0/"},{"subitem_rights":"Creative Commons Attribution 4.0 International","subitem_rights_language":"en","subitem_rights_resource":"https://creativecommons.org/licenses/by/4.0/"},{"subitem_rights":"© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/ ).","subitem_rights_language":"en"}]},"item_1617186609386":{"attribute_name":"主題","attribute_value_mlt":[{"subitem_subject":"C9orf72遺伝子","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"前頭側頭型認知症","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"筋萎縮性側索硬化症","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"異常伸長","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"異常タンパク質","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"リファンピシン","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"C9orf72","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"frontotemporal dementia (FTD)","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"amyotrophic lateral sclerosis (ALS)","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"hexanucleotide repeat expansion (HRE)","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"RNA foci","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"double-strand RNA-dependent protein kinase (PKR)","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"repeat-associated non-ATG (RAN) translation","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"dipeptide repeat protein (DPR)","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"TDP-43","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"rifampicin","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_1617186626617":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究グループは、リファンピシンの経鼻投与が前頭側頭型認知症(FTD)や筋萎縮性側索硬化症(ALS)にも有効であるとモデルマウスを用いた研究で明らかにしました。本研究結果は、リファンピシンが神経変性疾患に広く有効な薬となる可能性を示しています。FTDやALSはいまだ有効な治療法のない神経変性疾患です。原因として最も多いのがC9orf72遺伝子の非翻訳領域に存在するヘキサヌクレオチド(GGGGCC)リピートが異常伸長(HRE)する変異です。これにより生み出された異常なRNAやタンパク質が凝集し、神経系に蓄積することで神経変性が起こると考えられています。今回、本研究グループは、HREを有するC9orf72遺伝子発現モデルマウスにリファンピシンを1カ月間経鼻投与し、マウスの認知機能を観察しました。その結果、リファンピシンを投与することでHREに起因する神経病理が抑制され、マウスの認知機能が改善することが明らかになりました。","subitem_description_language":"ja","subitem_description_type":"Abstract"},{"subitem_description":"The non-coding GGGGCC hexanucleotide repeat expansion (HRE) in C9orf72 gene is a dominant cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). This intronic mutation elicits the formation of nuclear and cytoplasmic inclusions containing RNA, RNA-binding proteins, and HRE-derived dipeptide repeat proteins (DPRs), leading to neurodegeneration via the gain-of-toxic function or loss-of-function of relevant proteins. Using C9-500 mice harboring ~500 repeats of the GGGGCC sequence in human C9orf72 gene, we investigated the effects of rifampicin against HRE-related pathological phenotypes. Rifampicin was administered intranasally to 4.5- to 5-month-old mice for 1 month, and their cognitive function and neuropathology were assessed by the Morris water maze test and immunohistochemical staining. Rifampicin treatment reduced the formation of RNA foci and cytoplasmic inclusions containing DPRs or phosphorylated TDP-43, and furthermore, the levels of phosphorylated double-strand RNA-dependent protein kinase (PKR) that regulates repeat-associated non-ATG (RAN) translation. Synapse loss in the hippocampus and neuronal loss and microglial activation in the prefrontal and motor cortices were also attenuated, and mouse memory was significantly improved. Our findings suggest a therapeutic potential of nasal rifampicin in the prevention of C9orf72-linked neurodegenerative disorders.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_1617186643794":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"MDPI","subitem_publisher_language":"en"}]},"item_1617186783814":{"attribute_name":"識別子","attribute_value_mlt":[{"subitem_identifier_type":"DOI","subitem_identifier_uri":"https://doi.org/10.3390/biomedicines10051080"}]},"item_1617186920753":{"attribute_name":"収録物識別子","attribute_value_mlt":[{"subitem_source_identifier":"2227-9059","subitem_source_identifier_type":"ISSN"}]},"item_1617187056579":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022-05-06","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"5","bibliographicPageStart":"1080","bibliographicVolumeNumber":"10","bibliographic_titles":[{"bibliographic_title":"Biomedicines","bibliographic_titleLang":"en"}]}]},"item_1617258105262":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"journal article","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_1617265215918":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_1722232185104":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-05-19"}],"displaytype":"detail","filename":"22279059-10-5-1080.pdf","filesize":[{"value":"7.4 MB"}],"format":"application/pdf","mimetype":"application/pdf","url":{"label":"本文","objectType":"fulltext","url":"https://ocu-omu.repo.nii.ac.jp/record/2019677/files/22279059-10-5-1080.pdf"},"version_id":"f71e703e-7199-44ca-b56a-d602da3de029"}]},"item_1722577087681":{"attribute_name":"記事種別等","attribute_value_mlt":[{"subitem_description":"Article","subitem_description_language":"en","subitem_description_type":"Other"}]},"item_1725590125188":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_title":"C9orf72 Hexanucleotide Repeat Expansion-Related Neuropathology Is Attenuated by Nasal Rifampicin in Mice","item_type_id":"40002","owner":"7","path":["1721355153493"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2022-05-19"},"publish_date":"2022-05-19","publish_status":"0","recid":"2019677","relation_version_is_last":true,"title":["C9orf72 Hexanucleotide Repeat Expansion-Related Neuropathology Is Attenuated by Nasal Rifampicin in Mice"],"weko_creator_id":"7","weko_shared_id":-1},"updated":"2024-10-31T00:55:02.712096+00:00"}