WEKO3
アイテム
{"_buckets": {"deposit": "00beda2c-374f-4810-9da5-24505c3f96fc"}, "_deposit": {"created_by": 2, "id": "2273", "owners": [2], "pid": {"revision_id": 0, "type": "depid", "value": "2273"}, "status": "published"}, "_oai": {"id": "oai:nagasaki-u.repo.nii.ac.jp:00002273", "sets": ["74"]}, "author_link": ["10544", "10545", "10543", "10546", "10547"], "item_2_biblio_info_6": {"attribute_name": "書誌情報", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2017-03-01", "bibliographicIssueDateType": "Issued"}, "bibliographicIssueNumber": "3", "bibliographicPageEnd": "333", "bibliographicPageStart": "327", "bibliographicVolumeNumber": "40", "bibliographic_titles": [{"bibliographic_title": "Biological \u0026 Pharmaceutical Bulletin"}]}]}, "item_2_description_4": {"attribute_name": "抄録", "attribute_value_mlt": [{"subitem_description": "Amyloid-β peptide (Aβ) accumulation is a triggering event leading to the Alzheimer\u0027s disease (AD) pathological cascade. Almost all familial AD-linked gene mutations increase Aβ production and accelerate the onset of AD. The Swedish mutation of amyloid precursor protein (APP) affects β-secretase activity and increases Aβ production up to ca. 6-fold in cultured cells; the onset age is around 50. Down syndrome (DS) patients with chromosome 21 trisomy present AD-like pathologies at earlier ages (40s) compared with sporadic AD patients, because APP gene expression is 1.5-fold higher than that in healthy people, thus causing a 1.5-fold increase in Aβ production. However, when comparing the causal relationship of Aβ accumulation with the onset age between the above two populations, early DS pathogenesis does not appear to be accounted for by the increased Aβ production alone. In this study, we found that neprilysin, a major Aβ-degrading enzyme, was downregulated in DS patient-derived fibroblasts, compared with healthy people-derived fibroblasts. Treatment with harmine, an inhibitor of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), which is located in the DS critical region of chromosome 21, and gene knockdown of DYRK1A, upregulated neprilysin in fibroblasts. These results suggest that a decrease in the Aβ catabolic rate may be, at least in part, one of the causes for accelerated AD-like pathogenesis in DS patients if a similar event occurs in the brains, and that neprilysin activity may be regulated directly or indirectly by DYRK1Amediated phosphorylation. DYRK1A inhibition may be a promising disease-modifying therapy for AD via neprilysin upregulation.", "subitem_description_type": "Abstract"}]}, "item_2_description_63": {"attribute_name": "引用", "attribute_value_mlt": [{"subitem_description": "Biological \u0026 Pharmaceutical Bulletin, 40(3), pp.327-333; 2017", "subitem_description_type": "Other"}]}, "item_2_publisher_33": {"attribute_name": "出版者", "attribute_value_mlt": [{"subitem_publisher": "日本薬学会"}]}, "item_2_relation_12": {"attribute_name": "DOI", "attribute_value_mlt": [{"subitem_relation_type": "isIdenticalTo", "subitem_relation_type_id": {"subitem_relation_type_id_text": "10.1248/bpb.b16-00825", "subitem_relation_type_select": "DOI"}}]}, "item_2_rights_13": {"attribute_name": "権利", "attribute_value_mlt": [{"subitem_rights": "c 2017 The Pharmaceutical Society of Japan"}]}, "item_2_source_id_7": {"attribute_name": "ISSN", "attribute_value_mlt": [{"subitem_source_identifier": "09186158", "subitem_source_identifier_type": "ISSN"}]}, "item_2_source_id_8": {"attribute_name": "EISSN", "attribute_value_mlt": [{"subitem_source_identifier": "13475215", "subitem_source_identifier_type": "ISSN"}]}, "item_2_text_62": {"attribute_name": "出版者別言語", "attribute_value_mlt": [{"subitem_text_value": "Pharmaceutical Society of Japan"}]}, "item_2_version_type_16": {"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": "Kawakubo, Takashi"}], "nameIdentifiers": [{"nameIdentifier": "10543", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Mori, Ryotaro"}], "nameIdentifiers": [{"nameIdentifier": "10544", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Shirotani, Keiro"}], "nameIdentifiers": [{"nameIdentifier": "10545", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Iwata, Nobuhisa"}], "nameIdentifiers": [{"nameIdentifier": "10546", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Asai, Masashi"}], "nameIdentifiers": [{"nameIdentifier": "10547", "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": "2020-12-21"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "BPBul40_327.pdf", "filesize": [{"value": "860.2 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": 860200.0, "url": {"label": "BPBul40_327.pdf", "url": "https://nagasaki-u.repo.nii.ac.jp/record/2273/files/BPBul40_327.pdf"}, "version_id": "0207528e-04e9-469d-aab6-1314bc707479"}]}, "item_keyword": {"attribute_name": "キーワード", "attribute_value_mlt": [{"subitem_subject": "Alzheimer\u0027s disease", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Chromosome 21", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Down syndrome", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Dual-specificity tyrosine phosphorylation-regulated kinase 1A", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Neprilysin", "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": "Neprilysin Is Suppressed by Dual-Specificity Tyrosine-Phosphorylation Regulated Kinase 1A (DYRK1A) in Down-Syndrome-Derived Fibroblasts", "item_titles": {"attribute_name": "タイトル", "attribute_value_mlt": [{"subitem_title": "Neprilysin Is Suppressed by Dual-Specificity Tyrosine-Phosphorylation Regulated Kinase 1A (DYRK1A) in Down-Syndrome-Derived Fibroblasts"}]}, "item_type_id": "2", "owner": "2", "path": ["74"], "permalink_uri": "http://hdl.handle.net/10069/37474", "pubdate": {"attribute_name": "公開日", "attribute_value": "2017-06-02"}, "publish_date": "2017-06-02", "publish_status": "0", "recid": "2273", "relation": {}, "relation_version_is_last": true, "title": ["Neprilysin Is Suppressed by Dual-Specificity Tyrosine-Phosphorylation Regulated Kinase 1A (DYRK1A) in Down-Syndrome-Derived Fibroblasts"], "weko_shared_id": -1}
Neprilysin Is Suppressed by Dual-Specificity Tyrosine-Phosphorylation Regulated Kinase 1A (DYRK1A) in Down-Syndrome-Derived Fibroblasts
http://hdl.handle.net/10069/37474
http://hdl.handle.net/10069/37474ec22b782-085b-42c8-a530-58c311a0120b
名前 / ファイル | ライセンス | アクション |
---|---|---|
BPBul40_327.pdf (860.2 kB)
|
|
Item type | 学術雑誌論文 / Journal Article(1) | |||||
---|---|---|---|---|---|---|
公開日 | 2017-06-02 | |||||
タイトル | ||||||
タイトル | Neprilysin Is Suppressed by Dual-Specificity Tyrosine-Phosphorylation Regulated Kinase 1A (DYRK1A) in Down-Syndrome-Derived Fibroblasts | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Alzheimer's disease | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Chromosome 21 | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Down syndrome | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Dual-specificity tyrosine phosphorylation-regulated kinase 1A | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Neprilysin | |||||
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 |
Kawakubo, Takashi
× Kawakubo, Takashi× Mori, Ryotaro× Shirotani, Keiro× Iwata, Nobuhisa× Asai, Masashi |
|||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Amyloid-β peptide (Aβ) accumulation is a triggering event leading to the Alzheimer's disease (AD) pathological cascade. Almost all familial AD-linked gene mutations increase Aβ production and accelerate the onset of AD. The Swedish mutation of amyloid precursor protein (APP) affects β-secretase activity and increases Aβ production up to ca. 6-fold in cultured cells; the onset age is around 50. Down syndrome (DS) patients with chromosome 21 trisomy present AD-like pathologies at earlier ages (40s) compared with sporadic AD patients, because APP gene expression is 1.5-fold higher than that in healthy people, thus causing a 1.5-fold increase in Aβ production. However, when comparing the causal relationship of Aβ accumulation with the onset age between the above two populations, early DS pathogenesis does not appear to be accounted for by the increased Aβ production alone. In this study, we found that neprilysin, a major Aβ-degrading enzyme, was downregulated in DS patient-derived fibroblasts, compared with healthy people-derived fibroblasts. Treatment with harmine, an inhibitor of dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), which is located in the DS critical region of chromosome 21, and gene knockdown of DYRK1A, upregulated neprilysin in fibroblasts. These results suggest that a decrease in the Aβ catabolic rate may be, at least in part, one of the causes for accelerated AD-like pathogenesis in DS patients if a similar event occurs in the brains, and that neprilysin activity may be regulated directly or indirectly by DYRK1Amediated phosphorylation. DYRK1A inhibition may be a promising disease-modifying therapy for AD via neprilysin upregulation. | |||||
書誌情報 |
Biological & Pharmaceutical Bulletin 巻 40, 号 3, p. 327-333, 発行日 2017-03-01 |
|||||
出版者 | ||||||
出版者 | 日本薬学会 | |||||
出版者別言語 | ||||||
Pharmaceutical Society of Japan | ||||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 09186158 | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 13475215 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1248/bpb.b16-00825 | |||||
権利 | ||||||
権利情報 | c 2017 The Pharmaceutical Society of Japan | |||||
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 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Biological & Pharmaceutical Bulletin, 40(3), pp.327-333; 2017 |