Outeiro, Tiago Fleming

[["dc.bibliographiccitation.firstpage","1270"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Current drug targets"],["dc.bibliographiccitation.lastpage","80"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","de Oliveira, Rita Machado"],["dc.contributor.author","Pais, Teresa F."],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2019-07-10T08:13:31Z"],["dc.date.available","2019-07-10T08:13:31Z"],["dc.date.issued","2010-10-01"],["dc.description.abstract","Aging has been a subject of interest since primordial times. More recently, it became clear that aging is the major known risk factor for several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease. A major focus in the field of aging is to examine whether the genetic regulators of lifespan also regulate the trigger and/or progression of age-related disorders. Sirtuins, which belong to the Sir2 family of NAD(+)-dependent deacetylases, are known to regulate longevity in yeast, worms, and flies. In mammals, there are seven homologs of the yeast Sir2, Sirt1-7. Therefore, the challenge now is to unravel howthe seven mammalian Sir2 proteins communicate to regulate the cross talk between aging and the onset and progression of age-related disorders. Here, we review how sirtuins contribute for aging and, in particular, for neurodegeneration and how they are becoming attractive targets for therapeutic intervention."],["dc.identifier.fs","577015"],["dc.identifier.pmid","20840069"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6055"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61267"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1873-5592"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.subject.mesh","Aging"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Disease Progression"],["dc.subject.mesh","Drug Delivery Systems"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Neurodegenerative Diseases"],["dc.subject.mesh","Risk Factors"],["dc.subject.mesh","Sirtuins"],["dc.title","Sirtuins: common targets in aging and in neurodegeneration."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["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"]]

[["dc.bibliographiccitation.firstpage","643"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Trends in biochemical sciences"],["dc.bibliographiccitation.lastpage","51"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Gonçalves, Susana A."],["dc.contributor.author","Matos, Joana E."],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2019-07-09T11:52:51Z"],["dc.date.available","2019-07-09T11:52:51Z"],["dc.date.issued","2010-11-01"],["dc.description.abstract","Several neurodegenerative diseases are characterized by the accumulation of misfolded and aggregated proteins, which lead to neurotoxicity. However, the nature of those toxic species is controversial. Developments in optical microscopy and live-cell imaging are essential in providing crucial insight into the molecular mechanisms involved. In particular, the technique of bimolecular fluorescence complementation (BiFC) represents a remarkable improvement for observing protein-protein interactions within living cells. Unlike other techniques, BiFC provides spatial and temporal resolution and can be carried out in a physiological environment. Among other applications, BiFC has been used to study molecular determinants of oligomerization in neurodegenerative disorders, thereby promising to unveil novel targets for therapeutics. We review the applicability of BiFC for investigating the molecular basis of neurodegenerative diseases associated with protein misfolding and aggregation."],["dc.identifier.doi","10.1016/j.tibs.2010.05.007"],["dc.identifier.fs","576699"],["dc.identifier.pmid","20561791"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6054"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60292"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","0968-0004"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Luminescent Proteins"],["dc.subject.mesh","Neurons"],["dc.subject.mesh","Protein Binding"],["dc.subject.mesh","Protein Folding"],["dc.subject.mesh","Protein Multimerization"],["dc.subject.mesh","Proteins"],["dc.title","Zooming into protein oligomerization in neurodegeneration using BiFC."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]