{"created":"2021-03-01T06:09:24.378903+00:00","id":5545,"links":{},"metadata":{"_buckets":{"deposit":"6b180dc5-539a-435b-abbf-2fd95209ca10"},"_deposit":{"id":"5545","owners":[],"pid":{"revision_id":0,"type":"depid","value":"5545"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:00005545","sets":["453:455","471:561:562"]},"item_6_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"Endogenous TDP-43 Overexpression with Disrupted Autoregulation : Toward an Amyotrophic Lateral Sclerosis Model"}]},"item_6_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2015-03-23","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"18","bibliographicPageStart":"1","bibliographic_titles":[{}]}]},"item_6_date_granted_51":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2015-03-23"}]},"item_6_degree_grantor_49":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"新潟大学"}]}]},"item_6_degree_name_48":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）"}]},"item_6_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"筋萎縮性側索硬化症 （amyotrophic lateral sclerosis: ALS）患者の運動神経細胞およびグリア細胞の細胞質内には，TAR DNA-binding protein 43kDa（TDP-43）陽性の封入体を認める．このTDP-43発現量が，ALS患者で亢進しているとの報告がある．一方，核内蛋白であるTDP-43は自己蛋白量調節機構を有しており，通常の状態ではこの過剰は起こり得ない．著者は，この自己蛋白量調節機構の破綻がTDP-43過剰発現および神経細胞障害を引き起こすとの仮説を立て，この自己蛋白量調節機構の破綻による内在性TDP-43過剰発現モデルを構築し，この仮説を検証することを本研究の目的とした．これまでに著者らは，外来性TDP-43過剰発現細胞の解析により，TDP-43エクソン6内の近位選択的イントロンのスプライシングが発現抑制に重要であることを示してきた．本研究では，この選択的スプライシングをモルフォリノアンチセンス核酸により特異的に抑制し，発現抑制機構を破綻させることにより，内在性TDP-43過剰発現状態を誘導することに成功した．さらに，成体マウス髄腔内へのアンチセンス核酸の投与により，脊髄組織においても内在性TDP-43発現を増加させた．これらの結果は，TDP-43発現抑制機構におけるこの選択的スプライシングの意義を決定づけるとともに，この破綻による内在性TDP-43過剰モデルを細胞およびマウス個体において構築したことを意味する．さらに，この内在性TDP-43過剰発現マウスでは，ALS罹患組織でみられるTDP-43 C末断片の増加，さらにアポトーシス促進因子であるBIMの発現増加を認めた．これらより，TDP-43エクソン6内の選択的スプライシング効率の減弱は，内在性TDP-43の過剰発現を導き，神経細胞障害を引き起こすことが示唆された．この内在性TDP-43過剰発現モデルが，ALS病態のさらなる解明と治療法開発に貢献することが期待される．","subitem_description_type":"Abstract"}]},"item_6_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"学位の種類: 博士（医学）. 報告番号: 甲第3974号. 学位記番号: 新大院博（医）甲第620号. 学位授与年月日: 平成27年3月23日","subitem_description_type":"Other"}]},"item_6_description_53":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"新大院博（医）甲第620号","subitem_description_type":"Other"}]},"item_6_dissertation_number_52":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"13101甲第3974号"}]},"item_6_full_name_3":{"attribute_name":"著者別名","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"50464","nameIdentifierScheme":"WEKO"}],"names":[{"name":"Sugai, Akihiro"}]}]},"item_6_publisher_7":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"新潟大学"}]},"item_6_select_19":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_select_item":"ETD"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"須貝, 章弘"}],"nameIdentifiers":[{"nameIdentifier":"50463","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":"2019-08-05"}],"displaytype":"detail","filename":"h26nmk620.pdf","filesize":[{"value":"913.8 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"本文","url":"https://niigata-u.repo.nii.ac.jp/record/5545/files/h26nmk620.pdf"},"version_id":"5cbd1c7b-1bd7-4c7b-bcc0-5786eab19dda"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2019-08-05"}],"displaytype":"detail","filename":"h26nmk620_a.pdf","filesize":[{"value":"206.4 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自己蛋白量調節機構の破綻による内在性TDP-43の過剰発現","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"筋萎縮性側索硬化症の病態モデル : 自己蛋白量調節機構の破綻による内在性TDP-43の過剰発現"},{"subitem_title":"筋萎縮性側索硬化症の病態モデル : 自己蛋白量調節機構の破綻による内在性TDP-43の過剰発現","subitem_title_language":"en"}]},"item_type_id":"6","owner":"1","path":["455","562"],"pubdate":{"attribute_name":"公開日","attribute_value":"2015-06-03"},"publish_date":"2015-06-03","publish_status":"0","recid":"5545","relation_version_is_last":true,"title":["筋萎縮性側索硬化症の病態モデル : 自己蛋白量調節機構の破綻による内在性TDP-43の過剰発現"],"weko_creator_id":"1","weko_shared_id":2},"updated":"2022-12-15T03:38:34.936437+00:00"}