Silva Guerreiro, Patricia da

[["dc.bibliographiccitation.firstpage","149"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.lastpage","161"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Yin, Guowei"],["dc.contributor.author","Da Fonseca, Tomas Lopes"],["dc.contributor.author","Eisbach, Sibylle E."],["dc.contributor.author","Anduaga, Ane Martin"],["dc.contributor.author","Breda, Carlo"],["dc.contributor.author","Orcellet, Maria L."],["dc.contributor.author","Szego, Eva M."],["dc.contributor.author","Guerreiro, Patricia"],["dc.contributor.author","Lazar, Diana F."],["dc.contributor.author","Braus, Gerhard H."],["dc.contributor.author","Fernandez, Claudio O."],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Goody, Roger S."],["dc.contributor.author","Itzen, Aymelt"],["dc.contributor.author","Giorgini, Flaviano"],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2017-09-07T11:45:30Z"],["dc.date.available","2017-09-07T11:45:30Z"],["dc.date.issued","2014"],["dc.description.abstract","Alpha-synuclein (alpha S) misfolding is associated with Parkinson's disease (PD) but little is known about the mechanisms underlying alpha S toxicity. Increasing evidence suggests that defects in membrane transport play an important role in neuronal dysfunction. Here we demonstrate that the GTPase Rab8a interacts with alpha S in rodent brain. NMR spectroscopy reveals that the C-terminus of alpha S binds to the functionally important switch region as well as the C-terminal tail of Rab8a. In line with a direct Rab8a/alpha S interaction, Rab8a enhanced alpha S aggregation and reduced alpha S-induced cellular toxicity. In addition, Rab8 - the Drosophila ortholog of Rab8a - ameliorated alpha S-oligomer specific locomotor impairment and neuron loss in fruit flies. In support of the pathogenic relevance of the alpha S-Rab8a interaction, phosphorylation of alpha S at S129 enhanced binding to Rab8a, increased formation of insoluble alpha S aggregates and reduced cellular toxicity. Our study provides novel mechanistic insights into the interplay of the GTPase Rab8a and alpha S cytotoxicity, and underscores the therapeutic potential of targeting this interaction. (C) 2014 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.nbd.2014.06.018"],["dc.identifier.gro","3142046"],["dc.identifier.isi","000340691400015"],["dc.identifier.pmid","24983211"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3945"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1095-953X"],["dc.relation.issn","0969-9961"],["dc.title","alpha-Synuclein interacts with the switch region of Rab8a in a Ser129 phosphorylation-dependent manner"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6732"],["dc.bibliographiccitation.issue","25"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","6745"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Chutna, Oldriska"],["dc.contributor.author","Goncalves, Susana A."],["dc.contributor.author","Villar-Pique, Anna"],["dc.contributor.author","Guerreiro, Patricia S."],["dc.contributor.author","Marijanovic, Zrinka"],["dc.contributor.author","Mendes, Tiago"],["dc.contributor.author","Ramalho, Jose S."],["dc.contributor.author","Emmanouilidou, Evangelia"],["dc.contributor.author","Ventura, Salvador"],["dc.contributor.author","Klucken, Jochen"],["dc.contributor.author","Barral, Duarte C."],["dc.contributor.author","Giorgini, Flaviano"],["dc.contributor.author","Vekrellis, Kostas"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T09:31:10Z"],["dc.date.available","2018-11-07T09:31:10Z"],["dc.date.issued","2014"],["dc.description.abstract","Alpha-synuclein (aSyn) misfolding and aggregation are pathological features common to several neurodegenerative diseases, including Parkinson's disease (PD). Mounting evidence suggests that aSyn can be secreted and transferred from cell to cell, participating in the propagation and spreading of pathological events. Rab11, a small GTPase, is an important regulator in both endocytic and secretory pathways. Here, we show that Rab11 is involved in regulating aSyn secretion. Rab11 knockdown or overexpression of either Rab11a wild-type (Rab11a WT) or Rab11a GDP-bound mutant (Rab11a S25N) increased secretion of aSyn. Furthermore, we demonstrate that Rab11 interacts with aSyn and is present in intracellular inclusions together with aSyn. Moreover, Rab11 reduces aSyn aggregation and toxicity. Our results suggest that Rab11 is involved in modulating the processes of aSyn secretion and aggregation, both of which are important mechanisms in the progression of aSyn pathology in PD and other synucleinopathies."],["dc.identifier.doi","10.1093/hmg/ddu391"],["dc.identifier.isi","000347923000004"],["dc.identifier.pmid","25092884"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31480"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1460-2083"],["dc.relation.issn","0964-6906"],["dc.title","The small GTPase Rab11 co-localizes with alpha-synuclein in intracellular inclusions and modulates its aggregation, secretion and toxicity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]