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In the canonical Notch signaling pathway, intramembrane cleavage by gamma-secretase serves to release an intracellular domain of Notch that shows activity in the nucleus through binding to transcription factors. Many type 1 transmembrane proteins, including Notch, Delta, and APP, have recently been shown to be substrates for gamma-secretase, and their intracellular domains are released from the cell membrane following cleavage by gamma-secretase. The common enzyme gamma-secretase modulates proteolysis and the turnover of possible signaling molecules, which has led to the attractive hypothesis that mechanisms similar to Notch signaling contribute widely to proteolysis-regulated signaling pathways. APP is also likely to have a signaling mechanism, although the physiological functions of APP have not been elucidated. Indeed, we have shown that the intracellular domain of APP alters gene expression and induces neuron-specific apoptosis. These results suggest that APP signaling responds to the onset of AD. Here, we review the possibility of gamma-secretase-regulated signaling, including APP signaling, which leads to AD."}]}, "item_creator": {"attribute_name": "\u8457\u8005", "attribute_type": "creator", "attribute_value_mlt": [{"creatorNames": [{"creatorName": "Nakayama,  Kohzo"}], "nameIdentifiers": [{"nameIdentifier": "6617", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Nagase,  Hisashi"}], "nameIdentifiers": [{"nameIdentifier": "6618", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Koh,  Chang-Sung"}], "nameIdentifiers": [{"nameIdentifier": "6619", "nameIdentifierScheme": "WEKO"}]}, {"creatorNames": [{"creatorName": "Ohkawara,  Takeshi"}], "nameIdentifiers": [{"nameIdentifier": "6620", "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": "2015-09-24"}], "displaytype": "detail", "download_preview_message": "", "file_order": 0, "filename": "gamma-Secretase-Regulated_Mechanisms_Similar_Notch_Signaling.pdf", "filesize": [{"value": "636.9 kB"}], "format": "application/pdf", "future_date_message": "", "is_thumbnail": false, "licensetype": "license_free", "mimetype": "application/pdf", "size": 636900.0, "url": {"label": "gamma-Secretase-Regulated_Mechanisms_Similar_Notch_Signaling.pdf", "url": "https://soar-ir.repo.nii.ac.jp/record/3729/files/gamma-Secretase-Regulated_Mechanisms_Similar_Notch_Signaling.pdf"}, "version_id": "24807595-b684-4d7e-9e48-66638b52dce0"}]}, "item_keyword": {"attribute_name": "\u30ad\u30fc\u30ef\u30fc\u30c9", "attribute_value_mlt": [{"subitem_subject": "Alzheimer\u0027s disease", "subitem_subject_scheme": "Other"}, {"subitem_subject": "gamma-Secretase", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Amyloid precursor protein", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Notch signaling", "subitem_subject_scheme": "Other"}, {"subitem_subject": "Intracellular domain", "subitem_subject_scheme": "Other"}]}, "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": "\u03b3-Secretase-Regulated Mechanisms Similar to Notch Signaling May Play a Role in Signaling Events, Including APP Signaling, Which Leads to Alzheimer\u0027s Disease", "item_titles": {"attribute_name": "\u30bf\u30a4\u30c8\u30eb", "attribute_value_mlt": [{"subitem_title": "\u03b3-Secretase-Regulated Mechanisms Similar to Notch Signaling May Play a Role in Signaling Events, Including APP Signaling, Which Leads to Alzheimer\u0027s Disease"}]}, "item_type_id": "6", "owner": "1", "path": ["461/462"], "permalink_uri": "http://hdl.handle.net/10091/17605", "pubdate": {"attribute_name": "\u516c\u958b\u65e5", "attribute_name_i18n": "\u516c\u958b\u65e5", "attribute_value": "2014-06-17"}, "publish_date": "2014-06-17", "publish_status": "0", "recid": "3729", "relation": {}, "relation_version_is_last": true, "title": ["\u03b3-Secretase-Regulated Mechanisms Similar to Notch Signaling May Play a Role in Signaling Events, Including APP Signaling, Which Leads to Alzheimer\u0027s Disease"], "weko_shared_id": 3}