{"created":"2023-06-20T14:15:22.284304+00:00","id":1634,"links":{},"metadata":{"_buckets":{"deposit":"7dea2863-6876-4ba6-b00d-76733f8b2f0c"},"_deposit":{"created_by":19,"id":"1634","owners":[19],"pid":{"revision_id":0,"type":"depid","value":"1634"},"status":"published"},"_oai":{"id":"oai:niu.repo.nii.ac.jp:00001634","sets":["3:4:85"]},"author_link":["5875","5876","5878","5877"],"item_10_biblio_info_7":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2022-03-31","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"185","bibliographicPageStart":"177","bibliographicVolumeNumber":"22","bibliographic_titles":[{"bibliographic_title":"長崎国際大学論叢"},{"bibliographic_title":"Nagasaki International University Review","bibliographic_titleLang":"en"}]}]},"item_10_creator_3":{"attribute_name":"著者別名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"MURASE, Hirotaka"}],"nameIdentifiers":[{"nameIdentifier":"5877","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"SASAKI, Shigeki"}],"nameIdentifiers":[{"nameIdentifier":"5878","nameIdentifierScheme":"WEKO"}]}]},"item_10_description_19":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_10_description_24":{"attribute_name":"Abstract","attribute_value_mlt":[{"subitem_description":"The repeating nucleic acid sequences play the important role in the gene regulations via the formation of the various higher-order structure, such as a stem-loop or a G-quadruplex structure.　However, the abnormal repeat-expansion, although its mechanism remains unclear, results in the intractable hereditary disease due to the onset of the toxicities in the nucleus and cytoplasm.　In many cases, the disease-cause repeat consists of ３ to ６ nucleotides and  forms the pathogenic higher-order structures when abnormally expanded.　There has been a great interest in the development of the small molecular therapeutic agents targeting the higher-order structure of repetitive nucleic acid, and some lead compounds have been found for the treatment of repeat diseases.　In this paper, we summarize examples of repeat expansion diseases, causative sequences, their symptomatic features, and describe the mechanism of toxicity directly caused by repeat expansions and approaches for the development of therapeutic agents.","subitem_description_type":"Other"}]},"item_10_description_5":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"遺伝子中に含まれるリピート配列は、ステムループ構造や G４ 重鎖構造など様々な高次構造を形成することで、遺伝子発現を制御する重要な因子として働くことが知られている。しかしながら、原因は未だ不明であるが、このリピート配列の異常伸長が生じると、核内や細胞質内にて様々な毒性が発生することになり、難治性の遺伝性疾患を引き起こす。疾患の原因となるリピート配列の多くは、３~６塩基程度の短いリピート単位であり、正常リピート域を超えると異常な高次構造が形成され疾患の原因となることが示されている。これまでに、核酸の高次構造を標的とした低分子治療薬の開発が盛んに研究されており、いくつかの分子はリピート病治療に向けたリード化合物として見出されている。本稿では、リピート病の疾患例やその症状の特徴、原因リピート配列などについてまとめ、リピート配列が直接的な原因となる毒性の発現機序や治療薬開発に向けたアプローチについて記述する。","subitem_description_type":"Abstract"}]},"item_10_publisher_8":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"長崎国際大学研究センター"}]},"item_10_select_26":{"attribute_name":"原稿区分","attribute_value_mlt":[{"subitem_select_item":"総説"}]},"item_10_source_id_11":{"attribute_name":"書誌レコードID","attribute_value_mlt":[{"subitem_source_identifier":"AA11766493","subitem_source_identifier_type":"NCID"}]},"item_10_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1346-4094","subitem_source_identifier_type":"ISSN"}]},"item_10_version_type_20":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"村瀬, 裕貴"},{"creatorName":"ムラセ, ヒロタカ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"5875","nameIdentifierScheme":"WEKO"}]},{"creatorNames":[{"creatorName":"佐々木, 茂貴"},{"creatorName":"ササキ, シゲキ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{"nameIdentifier":"5876","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2022-05-20"}],"displaytype":"detail","filename":"RN22-016.pdf","filesize":[{"value":"718.7 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"本文（PDF）","url":"https://niu.repo.nii.ac.jp/record/1634/files/RN22-016.pdf"},"version_id":"546e7278-4bb3-46ac-bedf-2fcbdb630c3f"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"リピート病","subitem_subject_scheme":"Other"},{"subitem_subject":"疾患原因配列","subitem_subject_scheme":"Other"},{"subitem_subject":"核酸高次構造","subitem_subject_scheme":"Other"},{"subitem_subject":"低分子リガンド","subitem_subject_scheme":"Other"},{"subitem_subject":"repeat expansion disease","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"causative sequences","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"DNA or RNA higher-order structure","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"small molecular ligand","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"リピート病の治療薬開発を目指した低分子創薬研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"リピート病の治療薬開発を目指した低分子創薬研究"},{"subitem_title":"Drug Discovery Research Toward the Small Molecular Therapeutic Agents for Repeat Expansion Diseases","subitem_title_language":"en"}]},"item_type_id":"10","owner":"19","path":["85"],"pubdate":{"attribute_name":"公開日","attribute_value":"2022-04-01"},"publish_date":"2022-04-01","publish_status":"0","recid":"1634","relation_version_is_last":true,"title":["リピート病の治療薬開発を目指した低分子創薬研究"],"weko_creator_id":"19","weko_shared_id":-1},"updated":"2023-07-21T05:53:05.919343+00:00"}