{"created":"2021-03-01T06:14:39.708929+00:00","id":10518,"links":{},"metadata":{"_buckets":{"deposit":"7aac2cc3-d08a-476a-b783-ff1d67d65f88"},"_deposit":{"id":"10518","owners":[],"pid":{"revision_id":0,"type":"depid","value":"10518"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:00010518","sets":["453:456","471:537:538:972"]},"item_7_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"Impaired Insulin Signal Transduction Promotes Alzheimer's Disease Pathology"}]},"item_7_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2009-12","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"12","bibliographicPageEnd":"630","bibliographicPageStart":"618","bibliographicVolumeNumber":"123","bibliographic_titles":[{"bibliographic_title":"新潟医学会雑誌"},{"bibliographic_title":"新潟医学会雑誌","bibliographic_titleLang":"en"}]}]},"item_7_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Alzheimer's disease (AD) is by far the most common form of dementia, and its prevalence is increasing all over the world. The pathology of AD is characterized by senile plaque and neurofibrillar tangle, which consist of β-amyloid (Aβ) and hyperphosphorylated tan, respectively. Although amyloid hypothesis in AD pathogenesis is widely accepted, the mechanisms how Aβ deposition leads to abnormal accumulation of hyperphosphorylated tau remain unclear. Recent epidemiological studies have suggested that there is a close association between AD and type 2 diabetes mellitus (T2DM). In this study, I investigated the molecular regulatory mechanisms of insulin signal transduction with special reference to AD pathology. When neuroblastoma-derived Neuro2a cells were treated with various concentrations of insulin, insulin receptor (IR) was proteolytically processed and extracellular Aβ was accumulated in a dose-dependent manner. Treating with high concentration of insulin resulted in impaired responses of phosphorylation of Akt and glycogen synthase kinase 3β (GSK3β) upon insulin stimulation, which is reminiscent of insulin resistance in T2DM. Interestingly, Neuro2a cells producing a large amount of intracellular Aβ showed the similar insulin resistance. Furthermore, when cells stably expressing human tau were coincubated with cells producing a large amount of Aβ, the levels of phosphorylated tau detected with the AT8 antibody were increased. These results suggest that Aβ accumulation might cause abnormal tau phosphorylation through impaired insulin signal transduction and that improvement of insulin signal transduction could be a new therapeutic target of AD treatment.","subitem_description_type":"Abstract"}]},"item_7_full_name_3":{"attribute_name":"著者別名","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"72021","nameIdentifierScheme":"WEKO"}],"names":[{"name":"Kasuga, Kensaku"}]}]},"item_7_publisher_7":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"新潟医学会"}]},"item_7_select_19":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_select_item":"publisher"}]},"item_7_source_id_11":{"attribute_name":"書誌レコードID","attribute_value_mlt":[{"subitem_source_identifier":"AN00182415","subitem_source_identifier_type":"NCID"}]},"item_7_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"00290440","subitem_source_identifier_type":"ISSN"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"春日, 健作"}],"nameIdentifiers":[{"nameIdentifier":"72020","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":"2019-08-06"}],"displaytype":"detail","filename":"123(12)_618-630.pdf","filesize":[{"value":"1.9 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"123(12)_618-630.pdf","url":"https://niigata-u.repo.nii.ac.jp/record/10518/files/123(12)_618-630.pdf"},"version_id":"bb8f362c-92f4-424b-b796-50de39ab168f"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Alzheimer's disease (AD)","subitem_subject_scheme":"Other"},{"subitem_subject":"Insulin signal transduction","subitem_subject_scheme":"Other"},{"subitem_subject":"Presenilin 1 (PS1)","subitem_subject_scheme":"Other"},{"subitem_subject":"β-Amyloid (Aβ)","subitem_subject_scheme":"Other"},{"subitem_subject":"phosphorylated tau","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"インスリンシグナル伝達障害がアルツハイマー病に及ぼす影響","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"インスリンシグナル伝達障害がアルツハイマー病に及ぼす影響"},{"subitem_title":"インスリンシグナル伝達障害がアルツハイマー病に及ぼす影響","subitem_title_language":"en"}]},"item_type_id":"7","owner":"1","path":["456","972"],"pubdate":{"attribute_name":"公開日","attribute_value":"2014-07-22"},"publish_date":"2014-07-22","publish_status":"0","recid":"10518","relation_version_is_last":true,"title":["インスリンシグナル伝達障害がアルツハイマー病に及ぼす影響"],"weko_creator_id":"1","weko_shared_id":null},"updated":"2022-12-15T03:46:23.169755+00:00"}