{"created":"2023-06-19T10:44:06.930903+00:00","id":4501,"links":{},"metadata":{"_buckets":{"deposit":"1860610b-1dc6-4abe-adcb-77e52270d5fc"},"_deposit":{"created_by":11,"id":"4501","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"4501"},"status":"published"},"_oai":{"id":"oai:shiga-med.repo.nii.ac.jp:00004501","sets":["30:389:390"]},"author_link":["8816","6573","6484","9403","8318","4013","8813","8817"],"item_4_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2023-07-23","bibliographicIssueDateType":"Issued"},"bibliographicPageEnd":"75","bibliographicPageStart":"68","bibliographicVolumeNumber":"666","bibliographic_titles":[{},{"bibliographic_title":"Biochemical and biophysical research communications","bibliographic_titleLang":"en"}]}]},"item_4_creator_3":{"attribute_name":"著者別名","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"松井, 温哉"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"林, 大貴"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"田口, 弘康"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"成瀬, 延康"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"目良, 裕"}],"nameIdentifiers":[{},{}]}]},"item_4_description_14":{"attribute_name":"フォーマット","attribute_value_mlt":[{"subitem_description":"application/pdf","subitem_description_type":"Other"}]},"item_4_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Alzheimer's disease is a neurologic disorder characterized by the accumulation of extracellular deposits of amyloid-β (Aβ) fibrils in the brain of patients. The key etiologic agent in Alzheimer's disease is not known; however oligomeric Aβ appears detrimental to neuronal functions and increases Aβ fibrils deposition. Previous research has shown that curcumin, a phenolic pigment of turmeric, has an effect on Aβ assemblies, although the mechanism remains unclear. In this study, we demonstrate that curcumin disassembles pentameric oligomers made from synthetic Aβ42 peptides (pentameric oAβ42), using atomic force microscopy imaging followed by Gaussian analysis. Since curcumin shows keto-enol structural isomerism (tautomerism), the effect of keto-enol tautomerism on its disassembly was investigated. We have found that curcumin derivatives capable of keto-enol tautomerization also disassemble pentameric oAβ42, while, a curcumin derivative incapable of tautomerization did not affect the integrity of pentameric oAβ42. These experimental findings indicate that keto-enol tautomerism plays an essential role in the disassembly. We propose a mechanism for oAβ42 disassembly by curcumin based on molecular dynamics calculations of the tautomerism. When curcumin and its derivatives bind to the hydrophobic regions of oAβ42, the keto-form changes predominantly to the enol-form; this transition is associated with structural (twisting, planarization and rigidification) and potential energy changes that give curcumin enough force to act as a torsion molecular-spring that eventually disassembles pentameric oAβ42. This proposed mechanism sheds new light on keto-enol tautomerism as a relevant chemical feature for designing such novel therapeutic drugs that target protein aggregation. ","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_publisher_32":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"Elsevier B.V."}]},"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":"37178507","subitem_relation_type_select":"PMID"}}]},"item_4_relation_11":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"10.1016/j.bbrc.2023.04.076"}],"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1016/j.bbrc.2023.04.076","subitem_relation_type_select":"DOI"}}]},"item_4_rights_12":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"© 2023 The Authors. Published by Elsevier Inc. All rights reserved. "}]},"item_4_source_id_7":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"1090-2104","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":"MATSUI, Atsuya"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"BELLIER, Jean-Pierre"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"HAYASHI, Daiki"}],"nameIdentifiers":[{}]},{"creatorNames":[{"creatorName":"ISHIBE, Takafumi"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"NAKAMURA, Yoshiaki"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"TAGUCHI, Hiroyasu"}],"nameIdentifiers":[{},{}]},{"creatorNames":[{"creatorName":"NARUSE, Nobuyasu"}],"nameIdentifiers":[{},{},{}]},{"creatorNames":[{"creatorName":"MERA, Yutaka"}],"nameIdentifiers":[{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2023-06-05"}],"displaytype":"detail","filename":"j.bbrc.2023.04.076.pdf","filesize":[{"value":"1.7 MB"}],"format":"application/pdf","license_note":"This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"j.bbrc.2023.04.076","url":"https://shiga-med.repo.nii.ac.jp/record/4501/files/j.bbrc.2023.04.076.pdf"},"version_id":"c640a510-dab1-4234-984a-7c142c566c49"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Amyloid-β","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Oligomers","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Curcumin","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Atomic force microscopy","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Tautomerism","subitem_subject_language":"en","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":"Curcumin tautomerization in the mechanism of pentameric amyloid- β42 oligomers disassembly.","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Curcumin tautomerization in the mechanism of pentameric amyloid- β42 oligomers disassembly."}]},"item_type_id":"4","owner":"11","path":["390"],"pubdate":{"attribute_name":"公開日","attribute_value":"2023-06-05"},"publish_date":"2023-06-05","publish_status":"0","recid":"4501","relation_version_is_last":true,"title":["Curcumin tautomerization in the mechanism of pentameric amyloid- β42 oligomers disassembly."],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2023-06-19T11:06:16.451819+00:00"}