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Prion-like Propagation of alpha-Synuclein Is Regulated by the FcgammaRIIB-SHP-1/2 Signaling Pathway in Neurons

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dc.contributor.authorChoi, YR-
dc.contributor.authorCha, SH-
dc.contributor.authorKang, SJ-
dc.contributor.authorKim, JB-
dc.contributor.authorJou, I-
dc.contributor.authorPark, SM-
dc.date.accessioned2019-11-13T04:27:21Z-
dc.date.available2019-11-13T04:27:21Z-
dc.date.issued2018-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/17563-
dc.description.abstractRecent evidence of prion-like propagation of alpha-synuclein (alpha-syn) into neighboring neurons set up a paradigm to elucidate the mechanism of progression of Parkinson's disease (PD) and to develop therapeutic strategies. Here, we show that FcgammaRIIB expressed in neurons functions as a receptor for alpha-syn fibrils and mediates cell-to-cell transmission of alpha-syn. SHP-1 and 2 are activated downstream by alpha-syn fibrils through FcgammaRIIB and play an important role in cell-to-cell transmission of alpha-syn. Also, taking advantage of a co-culture system, we show that cell-to-cell transmission of alpha-syn induces intracellular Lewy body-like inclusion body formation and that the FcgammaRIIB/SHP-1/2 signaling pathway is involved in it. Therefore, the FcgammaRIIB-SHP-1/-2 signaling pathway may be a therapeutic target for the progression of PD. The in vitro system is an efficient tool for further high-throughput screening that can be used for developing a therapeutic intervention in PD.-
dc.language.isoen-
dc.subject.MESHCell Line-
dc.subject.MESHHumans-
dc.subject.MESHNeurons/metabolism-
dc.subject.MESHNeurons/pathology-
dc.subject.MESHParkinson Disease/genetics-
dc.subject.MESHParkinson Disease/metabolism-
dc.subject.MESHParkinson Disease/pathology-
dc.subject.MESHPrions-
dc.subject.MESHProtein Transport/genetics-
dc.subject.MESHProtein Tyrosine Phosphatase, Non-Receptor Type 11/genetics-
dc.subject.MESHProtein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism-
dc.subject.MESHProtein Tyrosine Phosphatase, Non-Receptor Type 6/genetics-
dc.subject.MESHProtein Tyrosine Phosphatase, Non-Receptor Type 6/metabolism-
dc.subject.MESHReceptors, IgG/genetics-
dc.subject.MESHReceptors, IgG/metabolism-
dc.subject.MESHSignal Transduction-
dc.subject.MESHalpha-Synuclein/genetics-
dc.subject.MESHalpha-Synuclein/metabolism-
dc.titlePrion-like Propagation of alpha-Synuclein Is Regulated by the FcgammaRIIB-SHP-1/2 Signaling Pathway in Neurons-
dc.typeArticle-
dc.identifier.pmid29298416-
dc.contributor.affiliatedAuthor주, 일로-
dc.contributor.affiliatedAuthor박, 상면-
dc.type.localJournal Papers-
dc.identifier.doi10.1016/j.celrep.2017.12.009-
dc.citation.titleCell reports-
dc.citation.volume22-
dc.citation.number1-
dc.citation.date2018-
dc.citation.startPage136-
dc.citation.endPage148-
dc.identifier.bibliographicCitationCell reports, 22(1). : 136-148, 2018-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissn2211-1247-
dc.relation.journalidJ022111247-
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
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