{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360004239504072448.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.3390/medsci4030014"}},{"identifier":{"@type":"URI","@value":"https://www.mdpi.com/2076-3271/4/3/14/pdf"}},{"identifier":{"@type":"PMID","@value":"29083378"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"Neuroprotection by Endoplasmic Reticulum Stress-Induced HRD1 and Chaperones: Possible Therapeutic Targets for Alzheimer’s and Parkinson’s Disease"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Alzheimer’s disease (AD) and Parkinson’s disease (PD) are neurodegenerative disorders with a severe medical and social impact. Further insights from clinical and scientific studies are essential to develop effective therapies. Various stresses on the endoplasmic reticulum (ER) cause unfolded/misfolded proteins to aggregate, initiating unfolded protein responses (UPR), one of which is the induction of neuronal cell death. Some of the pathogenic factors for AD and PD are associated with UPR. ER molecules such as ubiquitin ligases (E3s) and chaperones are also produced during UPR to degrade and refold aberrant proteins that accumulate in the ER. In this review, we examine the role of HMG-CoA reductase degradation protein 1 (HRD1) and the chaperone protein-disulfide isomerase (PDI), which are both produced in the ER in response to stress. We discuss the importance of HRD1 in degrading amyloid precursor protein (APP) and Parkin-associated endothelin receptor-like receptor (Pael-R) to protect against neuronal death. PDI and the chemical chaperone 4-phenyl-butyrate also exert neuroprotective effects. We discuss the pathophysiological roles of ER stress, UPR, and the induction and neuroprotective effects of HRD1 and PDI, which may represent significant targets for novel AD and PD therapies.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380004239504072323","@type":"Researcher","foaf:name":[{"@value":"Jun Nomura"}],"jpcoar:affiliationName":[{"@value":"RIKEN Brain Research Institute, Saitama 351-0198, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1420282801186172416","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"40379889"},{"@type":"NRID","@value":"1000040379889"},{"@type":"NRID","@value":"9000267810069"},{"@type":"NRID","@value":"9000005278062"},{"@type":"NRID","@value":"9000267806004"},{"@type":"NRID","@value":"9000021810114"},{"@type":"NRID","@value":"9000324992745"},{"@type":"NRID","@value":"9000283281281"},{"@type":"NRID","@value":"9000345398613"},{"@type":"NRID","@value":"9000314379085"},{"@type":"NRID","@value":"9000019987319"},{"@type":"NRID","@value":"9000375905544"},{"@type":"NRID","@value":"9000362198264"},{"@type":"NRID","@value":"9000001196378"},{"@type":"NRID","@value":"9000019092834"},{"@type":"NRID","@value":"9000020833815"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0065390"}],"foaf:name":[{"@value":"Toru Hosoi"}],"jpcoar:affiliationName":[{"@value":"Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1420845751158295552","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"10322827"},{"@type":"NRID","@value":"1000010322827"},{"@type":"NRID","@value":"9000314057334"},{"@type":"NRID","@value":"9000021806889"},{"@type":"NRID","@value":"9000408808154"},{"@type":"NRID","@value":"9000021810104"},{"@type":"NRID","@value":"9000406380266"},{"@type":"NRID","@value":"9000263064461"},{"@type":"NRID","@value":"9000412604297"},{"@type":"NRID","@value":"9000321635945"},{"@type":"NRID","@value":"9000365543010"},{"@type":"NRID","@value":"9000411832632"},{"@type":"NRID","@value":"9000257820937"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0103544"}],"foaf:name":[{"@value":"Masayuki Kaneko"}],"jpcoar:affiliationName":[{"@value":"Department of Biochemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004239504072192","@type":"Researcher","foaf:name":[{"@value":"Koichiro Ozawa"}],"jpcoar:affiliationName":[{"@value":"Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004239504072450","@type":"Researcher","foaf:name":[{"@value":"Akinori Nishi"}],"jpcoar:affiliationName":[{"@value":"Department of Pharmacology, Kurume University School of Medicine, Kurume 830-0011, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004239504072321","@type":"Researcher","foaf:name":[{"@value":"Yasuyuki Nomura"}],"jpcoar:affiliationName":[{"@value":"Department of Pharmacology, Kurume University School of Medicine, Kurume 830-0011, Japan"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"20763271"}],"prism:publicationName":[{"@value":"Medical Sciences"}],"dc:publisher":[{"@value":"MDPI AG"}],"prism:publicationDate":"2016-08-18","prism:volume":"4","prism:number":"3","prism:startingPage":"14"},"reviewed":"false","dcterms:accessRights":"http://purl.org/coar/access_right/c_abf2","dc:rights":["https://creativecommons.org/licenses/by/4.0/"],"url":[{"@id":"https://www.mdpi.com/2076-3271/4/3/14/pdf"}],"createdAt":"2016-08-18","modifiedAt":"2025-10-11","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=R","dc:title":"R"},{"@id":"https://cir.nii.ac.jp/all?q=Review","dc:title":"Review"},{"@id":"https://cir.nii.ac.jp/all?q=molecular%20chaperone","dc:title":"molecular chaperone"},{"@id":"https://cir.nii.ac.jp/all?q=therapeutic%20development","dc:title":"therapeutic development"},{"@id":"https://cir.nii.ac.jp/all?q=unfolded%20protein%20responses","dc:title":"unfolded protein responses"},{"@id":"https://cir.nii.ac.jp/all?q=degradation/refolding%20of%20misfolded%20proteins","dc:title":"degradation/refolding of misfolded proteins"},{"@id":"https://cir.nii.ac.jp/all?q=endoplasmic%20reticulum","dc:title":"endoplasmic reticulum"},{"@id":"https://cir.nii.ac.jp/all?q=HRD1","dc:title":"HRD1"},{"@id":"https://cir.nii.ac.jp/all?q=Parkinson%E2%80%99s%20disease","dc:title":"Parkinson’s disease"},{"@id":"https://cir.nii.ac.jp/all?q=Medicine","dc:title":"Medicine"},{"@id":"https://cir.nii.ac.jp/all?q=Alzheimer%E2%80%99s%20disease","dc:title":"Alzheimer’s disease"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040282256843600896","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"15K21706"},{"@type":"JGN","@value":"JP15K21706"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15K21706/"}],"notation":[{"@language":"ja","@value":"ユビキチンリガーゼ破綻による神経変性疾患発症機構"},{"@language":"en","@value":"Pathogenic mechanism of neurodegenerative diseases associated with dysfunction of ubiquitin 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