{"created":"2023-07-27T06:50:13.490078+00:00","id":42922,"links":{},"metadata":{"_buckets":{"deposit":"3aa0a2bf-4ab3-4ab3-9e78-c70bccf153cd"},"_deposit":{"created_by":18,"id":"42922","owners":[18],"pid":{"revision_id":0,"type":"depid","value":"42922"},"status":"published"},"_oai":{"id":"oai:kanazawa-u.repo.nii.ac.jp:00042922","sets":["2812:2813:2826"]},"author_link":["68639","22241"],"item_9_biblio_info_8":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2008-04","bibliographicIssueDateType":"Issued"},"bibliographicPageStart":"7p.","bibliographicVolumeNumber":"2005-2007","bibliographic_titles":[{"bibliographic_title":"平成19(2007)年度 科学研究費補助金 基盤研究(C) 研究成果報告書"},{"bibliographic_title":"2007 Fiscal Year Final Research Report","bibliographic_titleLang":"en"}]}]},"item_9_creator_33":{"attribute_name":"著者別表示","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{}],"nameIdentifiers":[{},{}]}]},"item_9_description_21":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"パーキンソン病(PD)は黒質ドーパミン神経の選択的変性により、進行性の運動障害をきたす原因不明の神経変性疾患である。本研究において我々は、小胞体ストレス蛋白の一つORP150、若年性遺伝性パーキンソン病の原因遺伝子の一つであり、ユビキチン架橋酵素であるParkin、Parkinの基質として同定され、小胞体ストレスを誘起することが判明している蛋白質Pael受容体(Parkinassociated endothelin like receptor: PaelR)、更に、やはり小胞体を誘起することが判明している分泌系蛋白質Megsinを用いて、パーキンソニズムにおける小胞体ストレスの役割をより明らかにする事を目指した。アデノウイルスを用いて、PaelRをマウス線条体から逆行性に黒質緻密層(SNpc)に発現させた所、SNpc特異的に小胞体ストレス由来の神経細胞死が起こり、それらはGRP78やParkin等の小胞体関連蛋白の強制発現で改善されたが、HSP70など細胞質局在のストレス蛋白の強制発現では改善されなかった。また、小胞体ストレスモデル動物であるメグシン過剰発現ラット(Tg Meg rat)の海馬及びSNpcでは、神経細胞内凝集体の存在、小胞体ストレスの上昇に加えて、神経変性(神経細胞死)が観察された。このことから、SNpcの神経細胞が特に小胞体ストレスに対して脆弱であることが明らかになった。本研究を通じて、小胞体ストレスとパーキンソニズム発症の関連がより明らかになり、今後、小胞体ストレス制御による新しい神経保護法の開発が可能になると期待される。","subitem_description_type":"Abstract"},{"subitem_description":"Selective loss of dopaminergic neurons is the final common pathway in Parkinson's disease, the second most common neurodegenerative disorder. Selective neuronal expression of Pael-R(Parkin associated endothelin-like receptor)in mouse brain was achieved by injecting adenoviral vectors carrying a modified neuron-specific promoter and Cre-recombinase into the striatum. Upregulation of Pael-Receptor in the substantia nigra pars compacts (SNpc) of mice by retrograde infection induced endoplasmic reticulum(ER) stress lead to decreased levels of tyrosine hydroxylase and death of dopaminergic neurons. Neuronal cell death was not observed in the other areas of the brain projecting to/from the SNpc. The role of ER stress in dopaminergic neuronal vulnerability was highlighted by their decreased survival in mice deficient in the ubiquitin-protein ligase Parkin and the ER chaperone ORP150(150 kDa oxygen regulated protein), compared with their robust survival consequent to overexpression of either P arkin or an ER chaperone, 78 kDa glucose regulated protein (GRP78). Dopamine-related toxicity was also a key factor, as a dopamine synthetase inhibitor blocked neuronal death in parkin null mice. These data suggest a model in which ER- and dopamine-related slam are major contributors to decreased viability of dopaminergic neurons in a setting relevant to Parkinson's disease.\nFENIB (familial encephalopathy with neuroserpin inclusion bodies)is caused by intracellular accumulation/polymerization of mutant neuroserpins. Transgenic rats overexpressing megsin (Tg meg), a newly identified serine protease inhibitor (serpin), demonstrated intraneuronal periodic-acid Schiff (PAS)-positive inclusions distributed throughout deeper layers of cerebral cortex, CA1 of the hippocampus, and substantia nigra. Hippocampal extracts from Tg meg rats showed increased expression of ER stress proteins, and activation of caspases-12 & -3, associated with decreased neuronal density. Enhanced ER stress was also observed in dopaminergic neurons in the substantia nigra, in parallel with decreased neuronal viability and motor coordination. In each case, PAS-positive inclusions were also positive for megsin. These data suggest that overexpression of megsin results in ER stress, eventuating in the formation of PAS-positive inclusions. Tg meg rats provide a novel model relevant to FENIB in which accumulation of serpins in the ER induces selective dysfunction/loss of specific neuronal populations.","subitem_description_type":"Abstract"}]},"item_9_description_22":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"研究課題/領域番号:17500226, 研究期間(年度):2005-2007","subitem_description_type":"Other"},{"subitem_description":"出典：「小胞体ストレスとパーキンソニズム発症の関連に関する研究」研究成果報告書　課題番号17500226\n  (KAKEN：科学研究費助成事業データベース（国立情報学研究所）)\n　　　本文データは著者版報告書より作成","subitem_description_type":"Other"}]},"item_9_identifier_registration":{"attribute_name":"ID登録","attribute_value_mlt":[{"subitem_identifier_reg_text":"10.24517/00049271","subitem_identifier_reg_type":"JaLC"}]},"item_9_publisher_17":{"attribute_name":"公開者","attribute_value_mlt":[{"subitem_publisher":"金沢大学医学系研究科"}]},"item_9_relation_28":{"attribute_name":"関連URI","attribute_value_mlt":[{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/search/?qm=00019613"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/search/?qm=00019613","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17500226/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17500226/","subitem_relation_type_select":"URI"}},{"subitem_relation_name":[{"subitem_relation_name_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17500226/175002262007kenkyu_seika_hokoku_gaiyo/"}],"subitem_relation_type_id":{"subitem_relation_type_id_text":"https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17500226/175002262007kenkyu_seika_hokoku_gaiyo/","subitem_relation_type_select":"URI"}}]},"item_9_version_type_25":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_ab4af688f83e57aa","subitem_version_type":"AM"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2017-12-08"}],"displaytype":"detail","filename":"ME-PR-KITAO-Y-kaken 2008-7p.pdf","filesize":[{"value":"414.7 kB"}],"format":"application/pdf","licensetype":"license_11","mimetype":"application/pdf","url":{"label":"ME-PR-KITAO-Y-kaken 2008-7p.pdf","url":"https://kanazawa-u.repo.nii.ac.jp/record/42922/files/ME-PR-KITAO-Y-kaken 2008-7p.pdf"},"version_id":"84c8d697-c518-48fb-aaaa-44168d28e0ba"}]},"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":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"小胞体ストレスとパーキンソニズム発症の関連に関する研究","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"小胞体ストレスとパーキンソニズム発症の関連に関する研究"},{"subitem_title":"Endoplasmicreticulum(ER)stress and Parkinsonism","subitem_title_language":"en"}]},"item_type_id":"9","owner":"18","path":["2826"],"pubdate":{"attribute_name":"公開日","attribute_value":"2017-12-08"},"publish_date":"2017-12-08","publish_status":"0","recid":"42922","relation_version_is_last":true,"title":["小胞体ストレスとパーキンソニズム発症の関連に関する研究"],"weko_creator_id":"18","weko_shared_id":-1},"updated":"2023-07-27T14:24:43.048477+00:00"}