{"_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"}, "item_7_alternative_title_1": {"attribute_name": "\u305d\u306e\u4ed6\u306e\u30bf\u30a4\u30c8\u30eb", "attribute_value_mlt": [{"subitem_alternative_title": "Impaired Insulin Signal Transduction Promotes Alzheimer\u0027s Disease Pathology"}]}, "item_7_biblio_info_6": {"attribute_name": "\u66f8\u8a8c\u60c5\u5831", "attribute_value_mlt": [{"bibliographicIssueDates": {"bibliographicIssueDate": "2009-12", "bibliographicIssueDateType": "Issued"}, "bibliographicIssueNumber": "12", "bibliographicPageEnd": "630", "bibliographicPageStart": "618", "bibliographicVolumeNumber": "123", "bibliographic_titles": [{"bibliographic_title": "\u65b0\u6f5f\u533b\u5b66\u4f1a\u96d1\u8a8c"}, {"bibliographic_title": "\u65b0\u6f5f\u533b\u5b66\u4f1a\u96d1\u8a8c", "bibliographic_titleLang": "en"}]}]}, "item_7_description_4": {"attribute_name": "\u6284\u9332", "attribute_value_mlt": [{"subitem_description": "Alzheimer\u0027s 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 \u03b2-amyloid (A\u03b2) and hyperphosphorylated tan, respectively. Although amyloid hypothesis in AD pathogenesis is widely accepted, the mechanisms how A\u03b2 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 A\u03b2 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 3\u03b2 (GSK3\u03b2) upon insulin stimulation, which is reminiscent of insulin resistance in T2DM. Interestingly, Neuro2a cells producing a large amount of intracellular A\u03b2 showed the similar insulin resistance. Furthermore, when cells stably expressing human tau were coincubated with cells producing a large amount of A\u03b2, the levels of phosphorylated tau detected with the AT8 antibody were increased. These results suggest that A\u03b2 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": "\u8457\u8005\u5225\u540d", "attribute_value_mlt": [{"nameIdentifiers": [{"nameIdentifier": "72021", "nameIdentifierScheme": "WEKO"}], "names": [{"name": "Kasuga, Kensaku"}]}]}, "item_7_publisher_7": {"attribute_name": "\u51fa\u7248\u8005", "attribute_value_mlt": [{"subitem_publisher": "\u65b0\u6f5f\u533b\u5b66\u4f1a"}]}, "item_7_select_19": {"attribute_name": "\u8457\u8005\u7248\u30d5\u30e9\u30b0", "attribute_value_mlt": [{"subitem_select_item": "publisher"}]}, "item_7_source_id_11": {"attribute_name": "\u66f8\u8a8c\u30ec\u30b3\u30fc\u30c9ID", "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": "\u8457\u8005", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "\u6625\u65e5, \u5065\u4f5c"}], "nameIdentifiers": [{"nameIdentifier": "72020", "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": "2019-08-06"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "123(12)_618-630.pdf", "filesize": [{"value": "1.9 MB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": 1900000.0, "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": "\u30ad\u30fc\u30ef\u30fc\u30c9", "attribute_value_mlt": [{"subitem_subject": "Alzheimer\u0027s 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": "\u03b2-Amyloid (A\u03b2)", "subitem_subject_scheme": "Other"}, {"subitem_subject": "phosphorylated tau", "subitem_subject_scheme": "Other"}]}, "item_language": {"attribute_name": "\u8a00\u8a9e", "attribute_value_mlt": [{"subitem_language": "jpn"}]}, "item_resource_type": {"attribute_name": "\u8cc7\u6e90\u30bf\u30a4\u30d7", "attribute_value_mlt": [{"resourcetype": "departmental bulletin paper", "resourceuri": "http://purl.org/coar/resource_type/c_6501"}]}, "item_title": "\u30a4\u30f3\u30b9\u30ea\u30f3\u30b7\u30b0\u30ca\u30eb\u4f1d\u9054\u969c\u5bb3\u304c\u30a2\u30eb\u30c4\u30cf\u30a4\u30de\u30fc\u75c5\u306b\u53ca\u307c\u3059\u5f71\u97ff", "item_titles": {"attribute_name": "\u30bf\u30a4\u30c8\u30eb", "attribute_value_mlt": [{"subitem_title": "\u30a4\u30f3\u30b9\u30ea\u30f3\u30b7\u30b0\u30ca\u30eb\u4f1d\u9054\u969c\u5bb3\u304c\u30a2\u30eb\u30c4\u30cf\u30a4\u30de\u30fc\u75c5\u306b\u53ca\u307c\u3059\u5f71\u97ff"}, {"subitem_title": "\u30a4\u30f3\u30b9\u30ea\u30f3\u30b7\u30b0\u30ca\u30eb\u4f1d\u9054\u969c\u5bb3\u304c\u30a2\u30eb\u30c4\u30cf\u30a4\u30de\u30fc\u75c5\u306b\u53ca\u307c\u3059\u5f71\u97ff", "subitem_title_language": "en"}]}, "item_type_id": "7", "owner": "1", "path": ["453/456", "471/537/538/972"], "permalink_uri": "http://hdl.handle.net/10191/28591", "pubdate": {"attribute_name": "\u516c\u958b\u65e5", "attribute_value": "2014-07-22"}, "publish_date": "2014-07-22", "publish_status": "0", "recid": "10518", "relation": {}, "relation_version_is_last": true, "title": ["\u30a4\u30f3\u30b9\u30ea\u30f3\u30b7\u30b0\u30ca\u30eb\u4f1d\u9054\u969c\u5bb3\u304c\u30a2\u30eb\u30c4\u30cf\u30a4\u30de\u30fc\u75c5\u306b\u53ca\u307c\u3059\u5f71\u97ff"], "weko_shared_id": null}