{"_buckets": {"deposit": "fcae78c2-8a52-4593-8319-bf763427966a"}, "_deposit": {"id": "36496", "owners": [], "pid": {"revision_id": 0, "type": "depid", "value": "36496"}, "status": "published"}, "_oai": {"id": "oai:tsukuba.repo.nii.ac.jp:00036496"}, "item_5_biblio_info_6": {"attribute_name": "\u66f8\u8a8c\u60c5\u5831", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2015-11", "bibliographicIssueDateType": "Issued"}, "bibliographicPageStart": "73", "bibliographicVolumeNumber": "8", "bibliographic_titles": [{"bibliographic_title": "Molecular Brain"}]}]}, "item_5_creator_3": {"attribute_name": "\u8457\u8005\u5225\u540d", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "\u4fdd\u5742, \u611b"}], "nameIdentifiers": [{"nameIdentifier": "161696", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "70708453", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://nrid.nii.ac.jp/ja/nrid/1000070708453"}, {"nameIdentifier": "0000003410", "nameIdentifierScheme": "\u7b51\u6ce2\u5927\u5b66\u7814\u7a76\u8005\u7dcf\u89a7", "nameIdentifierURI": "http://trios.tsukuba.ac.jp/researcher/0000003410"}]}, {"creatorNames": [{"creatorName": "\u7389\u5ca1, \u6643"}], "nameIdentifiers": [{"nameIdentifier": "32", "nameIdentifierScheme": "WEKO"}, {"nameIdentifier": "50192183", "nameIdentifierScheme": "e-Rad", "nameIdentifierURI": "https://nrid.nii.ac.jp/ja/nrid/1000050192183"}, {"nameIdentifier": "0000001775", "nameIdentifierScheme": "\u7b51\u6ce2\u5927\u5b66\u7814\u7a76\u8005\u7dcf\u89a7", "nameIdentifierURI": "http://trios.tsukuba.ac.jp/researcher/0000001775"}]}]}, "item_5_description_4": {"attribute_name": "\u6284\u9332", "attribute_value_mlt": [{"subitem_description": "Background\n\u03b2-Site amyloid precursor protein cleaving enzyme 1 (BACE1) is a membrane-bound aspartyl protease that initiates amyloid \u03b2-protein (A\u03b2) generation. Aberrant elevation of BACE1 levels in brains of Alzheimer\u2019s disease (AD) patients may involve A\u03b2. In the present study, we used a neuron culture model system to investigate the effects of A\u03b2 on BACE1 expression as well as the underlying mechanisms.\n\nResults\nRat primary cortical neurons were treated with relatively low concentrations (2.5 \u03bcM) of A\u03b242 oligomers (A\u03b2-O) or fibrils (A\u03b2-F) for 2\u20133 days. A\u03b2-O induced a significant increase in protein levels of BACE1, while A\u03b2-F only had a marginal effect. Levels of amyloid precursor protein (APP) and the major \u03b1-secretase, ADAM10, remained unaltered upon treatment with both types of A\u03b2. A\u03b2-O treatment resulted in activation of eIF2\u03b1 and caspase 3 in a time-dependent manner, with no changes in the endoplasmic reticulum (ER) stress marker, GRP78, indicating that a typical ER stress response is not induced under our experimental conditions. Furthermore, A\u03b2-O did not affect BACE1 mRNA expression but augmented the levels of exogenous BACE1 expressed via recombinant adenoviruses, indicating regulation of BACE1 protein expression, not at the transcriptional or translational but the post-translational level. Immunocytochemical analysis revealed that A\u03b2-O causes a significant increase in BACE1 immunoreactivity in neurites (both axons and dendrites), but not soma of neurons; this change appears relevant to the mechanism of A\u03b2-O-induced BACE1 elevation, which may involve impairment of BACE1 trafficking and degradation. In contrast, A\u03b2-O had no effect on APP immunoreactivity.\n\nConclusion\nOur results collectively suggest that A\u03b2 oligomers induce BACE1 elevation via a post-translational mechanism involving its altered subcellular distribution in neurons, which possibly triggers a vicious cycle of A\u03b2 generation, thus contributing to the pathogenetic mechanism of AD.", "subitem_description_type": "Abstract"}]}, "item_5_publisher_27": {"attribute_name": "\u51fa\u7248\u8005", "attribute_value_mlt": [{"subitem_publisher": "BioMed Central"}]}, "item_5_relation_10": {"attribute_name": "PubMed\u756a\u53f7", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "26552445", "subitem_relation_type_select": "PMID"}}]}, "item_5_relation_11": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type_id": {"subitem_relation_type_id_text": "10.1186/s13041-015-0163-5", "subitem_relation_type_select": "DOI"}}]}, "item_5_rights_12": {"attribute_name": "\u6a29\u5229", "attribute_value_mlt": [{"subitem_rights": "\u00a9 2015 Mamada et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated."}]}, "item_5_select_15": {"attribute_name": "\u8457\u8005\u7248\u30d5\u30e9\u30b0", "attribute_value_mlt": [{"subitem_select_item": "publisher"}]}, "item_5_source_id_7": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "1756-6606", "subitem_source_identifier_type": "ISSN"}]}, "item_5_subject_20": {"attribute_name": "NII\u30b5\u30d6\u30b8\u30a7\u30af\u30c8", "attribute_value_mlt": [{"subitem_subject": "\u533b\u5b66", "subitem_subject_scheme": "Other"}]}, "item_creator": {"attribute_name": "\u8457\u8005", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Mamada, Naomi"}], "nameIdentifiers": [{"nameIdentifier": "124080", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Tanokashira, Daisuke"}], "nameIdentifiers": [{"nameIdentifier": "124081", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Hosaka, Ai"}], "nameIdentifiers": [{"nameIdentifier": "124082", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Kametani, Fuyuki"}], "nameIdentifiers": [{"nameIdentifier": "124083", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Tamaoka, Akira"}], "nameIdentifiers": [{"nameIdentifier": "124084", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Araki, Wataru"}], "nameIdentifiers": [{"nameIdentifier": "124085", "nameIdentifierScheme": "WEKO"}]}]}, "item_files": {"attribute_name": "\u30d5\u30a1\u30a4\u30eb\u60c5\u5831", "attribute_type": "file", "attribute_value_mlt": [{"accessrole": "open_date", "date": [{"dateType": "Available", "dateValue": "2015-12-28"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "MB_8.pdf", "filesize": [{"value": "2.0 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_6", "mimetype": "application/pdf", "size": 2000000.0, "url": {"label": "MB_8", "url": "https://tsukuba.repo.nii.ac.jp/record/36496/files/MB_8.pdf"}, "version_id": "9ef04d42-54a1-4da9-a6f0-33357f50a907"}]}, "item_language": {"attribute_name": "\u8a00\u8a9e", "attribute_value_mlt": [{"subitem_language": "eng"}]}, "item_resource_type": {"attribute_name": "\u8cc7\u6e90\u30bf\u30a4\u30d7", "attribute_value_mlt": [{"resourcetype": "journal article", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "Amyloid \u03b2-protein oligomers upregulate the \u03b2-secretase, BACE1, through a post-translational mechanism involving its altered subcellular distribution in neurons", "item_titles": {"attribute_name": "\u30bf\u30a4\u30c8\u30eb", "attribute_value_mlt": [{"subitem_title": "Amyloid \u03b2-protein oligomers upregulate the \u03b2-secretase, BACE1, through a post-translational mechanism involving its altered subcellular distribution in neurons"}]}, "item_type_id": "5", "owner": "1", "path": ["2780/335", "2780/4852", "3/62/5595/4851"], "permalink_uri": "http://hdl.handle.net/2241/00132094", "pubdate": {"attribute_name": "\u516c\u958b\u65e5", "attribute_value": "2015-12-28"}, "publish_date": "2015-12-28", "publish_status": "0", "recid": "36496", "relation": {}, "relation_version_is_last": true, "title": ["Amyloid \u03b2-protein oligomers upregulate the \u03b2-secretase, BACE1, through a post-translational mechanism involving its altered subcellular distribution in neurons"], "weko_shared_id": 5}