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Intracellular delivery of Parkin rescues neurons from accumulation of damaged mitochondria and pathological α-synuclein

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dc.contributor.author이필휴-
dc.date.accessioned2020-09-28T02:33:17Z-
dc.date.available2020-09-28T02:33:17Z-
dc.date.issued2020-04-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/179098-
dc.description.abstractParkinson's disease (PD) is a progressive neurodegenerative disorder characterized by mitochondrial dysfunction, Lewy body formation, and loss of dopaminergic neurons. Parkin, an E3 ubiquitin ligase, is thought to inhibit PD progression by removing damaged mitochondria and suppressing the accumulation of α-synuclein and other protein aggregates. The present study describes a protein-based therapy for PD enabled by the development of a cell-permeable Parkin protein (iCP-Parkin) with enhanced solubility and optimized intracellular delivery. iCP-Parkin recovered damaged mitochondria by promoting mitophagy and mitochondrial biogenesis and suppressed toxic accumulations of α-synuclein in cells and animals. Last, iCP-Parkin prevented and reversed declines in tyrosine hydroxylase and dopamine expression concomitant with improved motor function induced by mitochondrial poisons or enforced α-synuclein expression. These results point to common, therapeutically tractable features in PD pathophysiology, and suggest that motor deficits in PD may be reversed, thus providing opportunities for therapeutic intervention after the onset of motor symptoms.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherAmerican Association for the Advancement of Science-
dc.relation.isPartOfSCIENCE ADVANCES-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleIntracellular delivery of Parkin rescues neurons from accumulation of damaged mitochondria and pathological α-synuclein-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Neurology (신경과학교실)-
dc.contributor.googleauthorEunna Chung-
dc.contributor.googleauthorYoungsil Choi-
dc.contributor.googleauthorJiae Park-
dc.contributor.googleauthorWonheum Nah-
dc.contributor.googleauthorJaehyung Park-
dc.contributor.googleauthorYukdong Jung-
dc.contributor.googleauthorJoonno Lee-
dc.contributor.googleauthorHyunji Lee-
dc.contributor.googleauthorSoyoung Park-
dc.contributor.googleauthorSunyoung Hwang-
dc.contributor.googleauthorSeongcheol Kim-
dc.contributor.googleauthorJongseok Lee-
dc.contributor.googleauthorDongjae Min-
dc.contributor.googleauthorJunghwan Jo-
dc.contributor.googleauthorShinyoung Kang-
dc.contributor.googleauthorMinyong Jung-
dc.contributor.googleauthorPhil Hyu Lee-
dc.contributor.googleauthorH Earl Ruley-
dc.contributor.googleauthorDaewoong Jo-
dc.identifier.doi10.1126/sciadv.aba1193-
dc.contributor.localIdA03270-
dc.relation.journalcodeJ03735-
dc.identifier.eissn2375-2548-
dc.identifier.pmid32494688-
dc.contributor.alternativeNameLee, Phil Hyu-
dc.contributor.affiliatedAuthor이필휴-
dc.citation.volume6-
dc.citation.number18-
dc.citation.startPageeaba1193-
dc.identifier.bibliographicCitationSCIENCE ADVANCES, Vol.6(18) : eaba1193, 2020-04-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers

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