{"created":"2023-06-26T11:01:33.225451+00:00","id":2280,"links":{},"metadata":{"_buckets":{"deposit":"99b163bf-e993-4beb-a4c1-670d589db9e1"},"_deposit":{"created_by":30,"id":"2280","owners":[30],"pid":{"revision_id":0,"type":"depid","value":"2280"},"status":"published"},"_oai":{"id":"oai:oist.repo.nii.ac.jp:00002280","sets":["6:213"]},"author_link":["15132","15144","15128","15139","15145","15142","15147","15143","15131","15141","15136","15134","15129","15137","15135","15130","15138","15146","15140","15133"],"item_10001_biblio_info_7":{"attribute_name":"Bibliographic Information","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2021-08-10","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"3","bibliographicPageEnd":"505","bibliographicPageStart":"490","bibliographicVolumeNumber":"90","bibliographic_titles":[{},{"bibliographic_title":"Annals of Neurology","bibliographic_titleLang":"en"}]}]},"item_10001_creator_3":{"attribute_name":"Author","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Jo, Junghyun"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yang, Lin"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Tran, Hoang‐Dai"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yu, Weonjin"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Sun, Alfred Xuyang"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Chang, Ya Yin"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Jung, Byung Chul"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Lee, Seung‐Jae"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Saw, Tzuen Yih"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Xiao, Bin"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Khoo, Audrey Tze Ting"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Yaw, Lai‐Ping"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Xie, Jessica Jiaxin"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Lokman, Hidayat"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Ong, Wei‐Yi"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Lim, Grace Gui Yin"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Lim, Kah‐Leong"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Tan, Eng‐King"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Ng, Huck‐Hui"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"Je, Hyunsoo Shawn"}],"nameIdentifiers":[{}]}]},"item_10001_description_5":{"attribute_name":"Abstract","attribute_value_mlt":[{"subitem_description":"Objective\nWe utilized human midbrain-like organoids (hMLOs) generated from human pluripotent stem cells carrying glucocerebrosidase gene (GBA1) and α-synuclein (α-syn; SNCA) perturbations to investigate genotype-to-phenotype relationships in Parkinson disease, with the particular aim of recapitulating α-syn– and Lewy body–related pathologies and the process of neurodegeneration in the hMLO model.\nMethods\nWe generated and characterized hMLOs from GBA1−/− and SNCA overexpressing isogenic embryonic stem cells and also generated Lewy body–like inclusions in GBA1/SNCA dual perturbation hMLOs and conduritol-b-epoxide–treated SNCA triplication hMLOs.\nResults\nWe identified for the first time that the loss of glucocerebrosidase, coupled with wild-type α-syn overexpression, results in a substantial accumulation of detergent-resistant, β-sheet–rich α-syn aggregates and Lewy body–like inclusions in hMLOs. These Lewy body–like inclusions exhibit a spherically symmetric morphology with an eosinophilic core, containing α-syn with ubiquitin, and can also be formed in Parkinson disease patient–derived hMLOs. We also demonstrate that impaired glucocerebrosidase function promotes the formation of Lewy body–like inclusions in hMLOs derived from patients carrying the SNCA triplication.\nInterpretation\nTaken together, the data indicate that our hMLOs harboring 2 major risk factors (glucocerebrosidase deficiency and wild-type α-syn overproduction) of Parkinson disease provide a tractable model to further elucidate the underlying mechanisms for progressive Lewy body formation. \nANN NEUROL 2021;90:490–505","subitem_description_type":"Other"}]},"item_10001_publisher_8":{"attribute_name":"Publisher","attribute_value_mlt":[{"subitem_publisher":"Wiley Periodicals LLC on behalf of American Neurological Association."}]},"item_10001_relation_13":{"attribute_name":"PubMedNo.","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"info:pmid/34288055","subitem_relation_type_select":"PMID"}}]},"item_10001_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"info:doi/10.1002/ana.26166","subitem_relation_type_select":"DOI"}}]},"item_10001_relation_17":{"attribute_name":"Related site","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://onlinelibrary.wiley.com/doi/full/10.1002/ana.26166","subitem_relation_type_select":"URI"}}]},"item_10001_rights_15":{"attribute_name":"Rights","attribute_value_mlt":[{"subitem_rights":"© 2021 The Author(s)."}]},"item_10001_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0364-5134","subitem_source_identifier_type":"ISSN"},{"subitem_source_identifier":"1531-8249","subitem_source_identifier_type":"ISSN"}]},"item_10001_version_type_20":{"attribute_name":"Author's flag","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2021-09-14"}],"displaytype":"detail","filename":"Jo-2021-Lewy-bodylike-inclusions-in-human-m.pdf","filesize":[{"value":"11.2 MB"}],"format":"application/pdf","license_note":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (https://creativecommons.org/licenses/by-nc-nd/4.0/)","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"Jo-2021-Lewy-bodylike-inclusions-in-human-m","url":"https://oist.repo.nii.ac.jp/record/2280/files/Jo-2021-Lewy-bodylike-inclusions-in-human-m.pdf"},"version_id":"4380284d-60cd-4ee1-85a8-50dd6c6b11b7"}]},"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":"Lewy Body–like Inclusions in Human Midbrain Organoids Carrying Glucocerebrosidase and α‐Synuclein Mutations","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Lewy Body–like Inclusions in Human Midbrain Organoids Carrying Glucocerebrosidase and α‐Synuclein Mutations","subitem_title_language":"en"}]},"item_type_id":"10001","owner":"30","path":["213"],"pubdate":{"attribute_name":"公開日","attribute_value":"2021-09-14"},"publish_date":"2021-09-14","publish_status":"0","recid":"2280","relation_version_is_last":true,"title":["Lewy Body–like Inclusions in Human Midbrain Organoids Carrying Glucocerebrosidase and α‐Synuclein Mutations"],"weko_creator_id":"30","weko_shared_id":30},"updated":"2023-06-26T11:33:43.576071+00:00"}