{"created":"2021-03-01T06:15:09.760951+00:00","id":10988,"links":{},"metadata":{"_buckets":{"deposit":"49ecbbf5-7584-401b-86be-2e64be95c654"},"_deposit":{"id":"10988","owners":[],"pid":{"revision_id":0,"type":"depid","value":"10988"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:00010988","sets":["453:456","471:537:538:986"]},"item_7_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"Mutational Analysis of TAR DNA Binding Protein-43(TDP-43) for Amyotrophic Lateral Sclerosis"}]},"item_7_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2008-10","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"10","bibliographicPageEnd":"571","bibliographicPageStart":"560","bibliographicVolumeNumber":"122","bibliographic_titles":[{"bibliographic_title":"新潟医学会雑誌"},{"bibliographic_title":"新潟医学会雑誌","bibliographic_titleLang":"en"}]}]},"item_7_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"筋萎縮性側索硬化症(ALS)は, 上位および下位運動ニューロンが選択的に変性する致死性の神経変性疾患である. 病理では運動ニューロンの細胞質にユビキチン化されたskein like inclusionを認め, この構成蛋白はTDP-43である. しかし本症の病態機序におけるTDP-43の意義は明らかになっていない. 筆者は本症におけるTDP-43の意義を明らかとするために, SOD1変異陰性の家族性ALS(FALS) 16家系においてTDP-43変異の有無を検討した. その結果1家系2世代発症者3名にて1028番目の塩基AからGへの置換を認めた. 同塩基置換は343番目のアミノ酸のグルタミンからアルギニンへの置換を伴い (Q343R), 同部は哺乳類で高度に保存されていた. また正常対称者267人でこの変異を認めなかった. この家系は病理所見でBunina小体, skein like inclusionを伴い, さらに広汎な孤発性ALSと同程度のTDP-43陽性細胞内封入体を認めた. また患者剖検脊髄を用いたウエスタンブロット解析では既報の孤発性ALSと同様に約25kDaの断片化TDP-43を検出した. TDP-43は核蛋白であり, 一部Cajal小体に局在し, caspase3による切断によりC末の25kDa断片型が形成され, これが凝集体を形成する. GFPとの融合蛋白を用いた実験でQ343R変異は, 全長型TDP-43の細胞内局在, および25kDa断片型の凝集休形成能においてwild typeと差を認めなかった. しかし変異型TDP-43を強制発現した細胞においてCajal小体の数の減少を認めた. FALS症例におけるTDP-43の変異の発見は, 本症の病態機序の解明に寄与することが期待される.","subitem_description_type":"Abstract"}]},"item_7_full_name_3":{"attribute_name":"著者別名","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"74860","nameIdentifierScheme":"WEKO"}],"names":[{"name":"Yokoseki, Akio"}]}]},"item_7_publisher_7":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"新潟医学会"}]},"item_7_select_19":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_select_item":"publisher"}]},"item_7_source_id_11":{"attribute_name":"書誌レコードID","attribute_value_mlt":[{"subitem_source_identifier":"AN00182415","subitem_source_identifier_type":"NCID"}]},"item_7_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"00290440","subitem_source_identifier_type":"ISSN"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"横関, 明男"}],"nameIdentifiers":[{"nameIdentifier":"74859","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":"2019-08-06"}],"displaytype":"detail","filename":"122(10)_560-571.pdf","filesize":[{"value":"1.8 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"122(10)_560-571.pdf","url":"https://niigata-u.repo.nii.ac.jp/record/10988/files/122(10)_560-571.pdf"},"version_id":"60ccecd3-6fb2-4043-82c3-2b3de910d479"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"familial amyotrophic lateral sclerosis (FALS)","subitem_subject_scheme":"Other"},{"subitem_subject":"TAR DNA binding protein-43 (TDP-43)","subitem_subject_scheme":"Other"},{"subitem_subject":"missense mutation","subitem_subject_scheme":"Other"},{"subitem_subject":"Q343R","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":"筋萎縮性側索硬化症におけるTAR DNA binding protein-43(TDP-43)変異の検討","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"筋萎縮性側索硬化症におけるTAR DNA binding protein-43(TDP-43)変異の検討"},{"subitem_title":"筋萎縮性側索硬化症におけるTAR DNA binding protein-43(TDP-43)変異の検討","subitem_title_language":"en"}]},"item_type_id":"7","owner":"1","path":["456","986"],"pubdate":{"attribute_name":"公開日","attribute_value":"2014-07-17"},"publish_date":"2014-07-17","publish_status":"0","recid":"10988","relation_version_is_last":true,"title":["筋萎縮性側索硬化症におけるTAR DNA binding protein-43(TDP-43)変異の検討"],"weko_creator_id":"1","weko_shared_id":null},"updated":"2022-12-15T03:44:31.535922+00:00"}