Outeiro, Tiago Fleming

[["dc.bibliographiccitation.firstpage","715"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","The Journal of clinical investigation"],["dc.bibliographiccitation.lastpage","25"],["dc.bibliographiccitation.volume","121"],["dc.contributor.author","Hansen, Christian"],["dc.contributor.author","Angot, Elodie"],["dc.contributor.author","Bergström, Ann-Louise"],["dc.contributor.author","Steiner, Jennifer A."],["dc.contributor.author","Pieri, Laura"],["dc.contributor.author","Paul, Gesine"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Melki, Ronald"],["dc.contributor.author","Kallunki, Pekka"],["dc.contributor.author","Fog, Karina"],["dc.contributor.author","Li, Jia-Yi"],["dc.contributor.author","Brundin, Patrik"],["dc.date.accessioned","2012-08-01T13:59:22Z"],["dc.date.accessioned","2021-10-27T13:10:56Z"],["dc.date.available","2012-08-01T13:59:22Z"],["dc.date.available","2021-10-27T13:10:56Z"],["dc.date.issued","2011-02-01"],["dc.description.abstract","Post-mortem analyses of brains from patients with Parkinson disease who received fetal mesencephalic transplants show that α-synuclein-containing (α-syn-containing) Lewy bodies gradually appear in grafted neurons. Here, we explored whether intercellular transfer of α-syn from host to graft, followed by seeding of α-syn aggregation in recipient neurons, can contribute to this phenomenon. We assessed α-syn cell-to-cell transfer using microscopy, flow cytometry, and high-content screening in several coculture model systems. Coculturing cells engineered to express either GFP- or DsRed-tagged α-syn resulted in a gradual increase in double-labeled cells. Importantly, α-syn-GFP derived from 1 neuroblastoma cell line localized to red fluorescent aggregates in other cells expressing DsRed-α-syn, suggesting a seeding effect of transmitted α-syn. Extracellular α-syn was taken up by cells through endocytosis and interacted with intracellular α-syn. Next, following intracortical injection of recombinant α-syn in rats, we found neuronal uptake was attenuated by coinjection of an endocytosis inhibitor. Finally, we demonstrated in vivo transfer of α-syn between host cells and grafted dopaminergic neurons in mice overexpressing human α-syn. In summary, intercellularly transferred α-syn interacts with cytoplasmic α-syn and can propagate α-syn pathology. These results suggest that α-syn propagation is a key element in the progression of Parkinson disease pathology."],["dc.identifier.doi","10.1172/JCI43366"],["dc.identifier.fs","584075"],["dc.identifier.pmid","21245577"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7841"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/91545"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.issn","1558-8238"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Brain"],["dc.subject.mesh","Cell Transplantation"],["dc.subject.mesh","Cells, Cultured"],["dc.subject.mesh","Coculture Techniques"],["dc.subject.mesh","Culture Media, Conditioned"],["dc.subject.mesh","Dopamine"],["dc.subject.mesh","HEK293 Cells"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Lewy Bodies"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Neurons"],["dc.subject.mesh","Parkinson Disease"],["dc.subject.mesh","Rats"],["dc.subject.mesh","Recombinant Fusion Proteins"],["dc.subject.mesh","alpha-Synuclein"],["dc.title","α-Synuclein propagates from mouse brain to grafted dopaminergic neurons and seeds aggregation in cultured human cells."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]