WEKO3
アイテム
{"_buckets": {"deposit": "c53f2d06-cba8-4283-824e-41b01628f894"}, "_deposit": {"created_by": 11, "id": "3281", "owners": [11], "pid": {"revision_id": 0, "type": "depid", "value": "3281"}, "status": "published"}, "_oai": {"id": "oai:shiga-med.repo.nii.ac.jp:00003281", "sets": ["199"]}, "author_link": ["7237", "7331", "7329", "7326", "7324", "7327", "6171", "1957", "7228", "1956"], "item_4_biblio_info_6": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2018-04-16", "bibliographicIssueDateType": "Issued"}, "bibliographicIssueNumber": "1", "bibliographicPageStart": "6030", "bibliographicVolumeNumber": "8", "bibliographic_titles": [{"bibliographic_title": "Scientific Reports"}]}]}, "item_4_creator_3": {"attribute_name": "著者別名", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "漆谷, 真"}], "nameIdentifiers": [{"nameIdentifier": "1956", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "60332326", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=60332326"}, {"nameIdentifier": "0000-0003-2773-9836", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0003-2773-9836"}]}, {"creatorNames": [{"creatorName": "玉木, 良高"}], "nameIdentifiers": [{"nameIdentifier": "7331", "nameIdentifierScheme": "WEKO"}]}]}, "item_4_description_4": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "Aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) is implicated in the pathogenesis of sporadic and certain familial forms of amyotrophic lateral sclerosis (ALS), suggesting elimination of TDP-43 aggregates as a possible therapeutic strategy. Here we generated and investigated a single-chain variable fragment (scFv) derived from the 3B12A monoclonal antibody (MAb) that recognises D247 of the TDP-43 nuclear export signal, an epitope masked in the physiological state. In transfected HEK293A cells, 3B12A scFv recapitulated the affinity of the full-length MAb to mislocalised TDP-43 with a defective nuclear localising signal and to a TDP-43 inclusion mimic with cysteine-to-serine substitution at RRM1. Moreover, 3B12A scFv accelerated proteasome-mediated degradation of aggregated TDP-43, likely due to an endogenous PEST-like proteolytic signal sequence in the VH domain CDR2 region. Addition of the chaperone-mediated autophagy (CMA)-related signal to 3B12A scFv induced HSP70 transcription, further enhancing TDP-43 aggregate clearance and cell viability. The 3B12A scFv also reduced TDP-43 aggregates in embryonic mouse brain following in utero electroporation while causing no overt postnatal brain pathology or developmental anomalies. These results suggest that a misfolding-specific intrabody prone to synergistic proteolysis by proteasomal and autophagic pathways is a promising strategy for mitigation of TDP-43 proteinopathy in ALS.", "subitem_description_type": "Abstract"}]}, "item_4_description_42": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"subitem_description": "Journal Article", "subitem_description_type": "Other"}]}, "item_4_description_5": {"attribute_name": "内容記述", "attribute_value_mlt": [{"subitem_description": "筋萎縮性側索硬化症の異常凝集体を除去する治療抗体の開発に成功-ALS の根治治療への道を開く -\n滋賀医科大学プレスリリース. 2018-05-31", "subitem_description_type": "Other"}]}, "item_4_publisher_32": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "Springer Nature"}]}, "item_4_relation_10": {"attribute_name": "PubMed番号", "attribute_value_mlt": [{"subitem_relation_type": "isIdenticalTo", "subitem_relation_type_id": {"subitem_relation_type_id_text": "29662239", "subitem_relation_type_select": "PMID"}}]}, "item_4_relation_11": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type": "isIdenticalTo", "subitem_relation_type_id": {"subitem_relation_type_id_text": "10.1038/s41598-018-24463-3", "subitem_relation_type_select": "DOI"}}]}, "item_4_rights_12": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "© The Author(s) 2018 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/."}]}, "item_4_source_id_7": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "2045-2322", "subitem_source_identifier_type": "ISSN"}]}, "item_4_version_type_15": {"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": "TAMAKI, Yoshitaka"}], "nameIdentifiers": [{"nameIdentifier": "7331", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "SHODAI, Akemi"}], "nameIdentifiers": [{"nameIdentifier": "7324", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "MORIMURA, Toshifumi"}], "nameIdentifiers": [{"nameIdentifier": "6171", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "20333338", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=20333338"}]}, {"creatorNames": [{"creatorName": "HIKIAMI, Ryota"}], "nameIdentifiers": [{"nameIdentifier": "7326", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "10885354", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=10885354"}]}, {"creatorNames": [{"creatorName": "MINAMIYAMA, Sumio"}], "nameIdentifiers": [{"nameIdentifier": "7327", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "FURUTA, Takahiro"}], "nameIdentifiers": [{"nameIdentifier": "7228", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "TOOYAMA, Ikuo"}], "nameIdentifiers": [{"nameIdentifier": "1957", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "20207533", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=20207533"}, {"nameIdentifier": "0000-0001-8054-9666", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0001-8054-9666"}]}, {"creatorNames": [{"creatorName": "FURUKAWA, Yoshiaki"}], "nameIdentifiers": [{"nameIdentifier": "7329", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "TAKAHASHI, Ryosuke"}], "nameIdentifiers": [{"nameIdentifier": "7237", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "90216771", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=90216771"}, {"nameIdentifier": "0000-0002-1407-9640", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0002-1407-9640"}]}, {"creatorNames": [{"creatorName": "URUSHITANI, Makoto"}], "nameIdentifiers": [{"nameIdentifier": "1956", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "60332326", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://kaken.nii.ac.jp/ja/search/?qm=60332326"}, {"nameIdentifier": "0000-0003-2773-9836", "nameIdentifierScheme": "ORCID", "nameIdentifierURI": "https://orcid.org/0000-0003-2773-9836"}]}]}, "item_files": {"attribute_name": "ファイル情報", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2018-06-01"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "s41598-018-24463-3.pdf", "filesize": [{"value": "11.7 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": 11700000.0, "url": {"label": "s41598-018-24463-3", "url": "https://shiga-med.repo.nii.ac.jp/record/3281/files/s41598-018-24463-3.pdf"}, "version_id": "dc9f78d3-5918-43f4-ba82-a984cf61f0eb"}]}, "item_keyword": {"attribute_name": "キーワード", "attribute_value_mlt": [{"subitem_subject": "Amyotrophic lateral sclerosis", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Cell death in the nervous system", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Molecular medicine", "subitem_subject_scheme": "Other"}]}, "item_language": {"attribute_name": "言語", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "資源タイプ", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Elimination of TDP-43 inclusions linked to amyotrophic lateral sclerosis by a misfolding-specific intrabody with dual proteolytic signals.", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Elimination of TDP-43 inclusions linked to amyotrophic lateral sclerosis by a misfolding-specific intrabody with dual proteolytic signals."}]}, "item_type_id": "4", "owner": "11", "path": ["199"], "permalink_uri": "http://hdl.handle.net/10422/00012419", "pubdate": {"attribute_name": "公開日", "attribute_value": "2018-06-01"}, "publish_date": "2018-06-01", "publish_status": "0", "recid": "3281", "relation": {}, "relation_version_is_last": true, "title": ["Elimination of TDP-43 inclusions linked to amyotrophic lateral sclerosis by a misfolding-specific intrabody with dual proteolytic signals."], "weko_shared_id": -1}
Elimination of TDP-43 inclusions linked to amyotrophic lateral sclerosis by a misfolding-specific intrabody with dual proteolytic signals.
http://hdl.handle.net/10422/00012419
http://hdl.handle.net/10422/00012419fbd9c9b0-b714-46cd-8bf9-09b1da6bd383
名前 / ファイル | ライセンス | アクション |
---|---|---|
s41598-018-24463-3 (11.7 MB)
|
|
Item type | 学術雑誌論文 / Journal Article(1) | |||||
---|---|---|---|---|---|---|
公開日 | 2018-06-01 | |||||
タイトル | ||||||
タイトル | Elimination of TDP-43 inclusions linked to amyotrophic lateral sclerosis by a misfolding-specific intrabody with dual proteolytic signals. | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Amyotrophic lateral sclerosis | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Cell death in the nervous system | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Molecular medicine | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
TAMAKI, Yoshitaka
× TAMAKI, Yoshitaka× SHODAI, Akemi× MORIMURA, Toshifumi× HIKIAMI, Ryota× MINAMIYAMA, Sumio× FURUTA, Takahiro× TOOYAMA, Ikuo× FURUKAWA, Yoshiaki× TAKAHASHI, Ryosuke× URUSHITANI, Makoto |
|||||
著者別名 |
漆谷, 真
× 漆谷, 真× 玉木, 良高 |
|||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Aggregation of TAR DNA-binding protein of 43 kDa (TDP-43) is implicated in the pathogenesis of sporadic and certain familial forms of amyotrophic lateral sclerosis (ALS), suggesting elimination of TDP-43 aggregates as a possible therapeutic strategy. Here we generated and investigated a single-chain variable fragment (scFv) derived from the 3B12A monoclonal antibody (MAb) that recognises D247 of the TDP-43 nuclear export signal, an epitope masked in the physiological state. In transfected HEK293A cells, 3B12A scFv recapitulated the affinity of the full-length MAb to mislocalised TDP-43 with a defective nuclear localising signal and to a TDP-43 inclusion mimic with cysteine-to-serine substitution at RRM1. Moreover, 3B12A scFv accelerated proteasome-mediated degradation of aggregated TDP-43, likely due to an endogenous PEST-like proteolytic signal sequence in the VH domain CDR2 region. Addition of the chaperone-mediated autophagy (CMA)-related signal to 3B12A scFv induced HSP70 transcription, further enhancing TDP-43 aggregate clearance and cell viability. The 3B12A scFv also reduced TDP-43 aggregates in embryonic mouse brain following in utero electroporation while causing no overt postnatal brain pathology or developmental anomalies. These results suggest that a misfolding-specific intrabody prone to synergistic proteolysis by proteasomal and autophagic pathways is a promising strategy for mitigation of TDP-43 proteinopathy in ALS. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 筋萎縮性側索硬化症の異常凝集体を除去する治療抗体の開発に成功-ALS の根治治療への道を開く - 滋賀医科大学プレスリリース. 2018-05-31 |
|||||
書誌情報 |
Scientific Reports 巻 8, 号 1, p. 6030, 発行日 2018-04-16 |
|||||
出版者 | ||||||
出版者 | Springer Nature | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2045-2322 | |||||
PMID | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | PMID | |||||
関連識別子 | 29662239 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1038/s41598-018-24463-3 | |||||
権利 | ||||||
権利情報 | © The Author(s) 2018 This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
資源タイプ | ||||||
内容記述タイプ | Other | |||||
内容記述 | Journal Article |