Outeiro, Tiago Fleming

[["dc.bibliographiccitation.journal","Yeast"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Tenreiro, Sandra"],["dc.contributor.author","Reimao-Pinto, Madalena M."],["dc.contributor.author","Antas, Pedro"],["dc.contributor.author","Rino, Jose"],["dc.contributor.author","Waiss, Meytal"],["dc.contributor.author","Magalhaes, Filipa"],["dc.contributor.author","Wawrzycka, Donata"],["dc.contributor.author","Macedo, Diana"],["dc.contributor.author","Cunha, Monica E."],["dc.contributor.author","Kaganovich, Daniel"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T09:20:11Z"],["dc.date.available","2018-11-07T09:20:11Z"],["dc.date.issued","2013"],["dc.format.extent","79"],["dc.identifier.isi","000327927400108"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28826"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.eventlocation","Frankfurt Main, GERMANY"],["dc.relation.issn","1097-0061"],["dc.relation.issn","0749-503X"],["dc.title","Harnessing the power of yeast to decipher the role of alpha-synuclein phosphorylation in Parkinson's disease"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.contributor.author","Brás, Inês Caldeira"],["dc.contributor.author","Khani, Mohammad Hossein"],["dc.contributor.author","Vasili, Eftychia"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Parfentev, Iwan"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Fahlbusch, Christiane"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Gollisch, Tim"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2022-02-23T16:36:34Z"],["dc.date.available","2022-02-23T16:36:34Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1101/2021.07.18.452825"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/100391"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/327"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/128"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation","SFB 1286 | B08: Definition von Kaskaden molekularer Veränderungen bei Synucleinopathien während der Neurodegeneration"],["dc.relation.workinggroup","RG Gollisch (Sensory Processing in the Retina)"],["dc.relation.workinggroup","RG Möbius"],["dc.relation.workinggroup","RG Outeiro (Experimental Neurodegeneration)"],["dc.relation.workinggroup","RG Urlaub (Bioanalytische Massenspektrometrie)"],["dc.title","Common molecular mechanisms underlie the transfer of alpha-synuclein, Tau and huntingtin and modulate spontaneous activity in neuronal cells"],["dc.type","preprint"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","E4971"],["dc.bibliographiccitation.issue","25"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America"],["dc.bibliographiccitation.lastpage","E4977"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Turriani, Elisa"],["dc.contributor.author","Lázaro, Diana F."],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Giese, Armin"],["dc.contributor.author","Schön, Margarete"],["dc.contributor.author","Schön, Michael P."],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Arndt-Jovin, Donna J."],["dc.contributor.author","Becker, Dorothea"],["dc.date.accessioned","2018-04-23T11:47:36Z"],["dc.date.available","2018-04-23T11:47:36Z"],["dc.date.issued","2017"],["dc.description.abstract","Recent epidemiological and clinical studies have reported a significantly increased risk for melanoma in people with Parkinson’s disease. Because no evidence could be obtained that genetic factors are the reason for the association between these two diseases, we hypothesized that of the three major Parkinson’s disease-related proteins—α-synuclein, LRRK2, and Parkin—α-synuclein might be a major link. Our data, presented here, demonstrate that α-synuclein promotes the survival of primary and metastatic melanoma cells, which is the exact opposite of the effect that α-synuclein has on dopaminergic neurons, where its accumulation causes neuronal dysfunction and death. Because this detrimental effect of α-synuclein on neurons can be rescued by the small molecule anle138b, we explored its effect on melanoma cells. We found that treatment with anle138b leads to massive melanoma cell death due to a major dysregulation of autophagy, suggesting that α-synuclein is highly beneficial to advanced melanoma because it ensures that autophagy is maintained at a homeostatic level that promotes and ensures the cell’s survival."],["dc.identifier.doi","10.1073/pnas.1700200114"],["dc.identifier.gro","3142238"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13362"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0027-8424"],["dc.title","Treatment with diphenyl–pyrazole compound anle138b/c reveals that α-synuclein protects melanoma cells from autophagic cell death"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","693"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Journal of Molecular Medicine"],["dc.bibliographiccitation.lastpage","703"],["dc.bibliographiccitation.volume","91"],["dc.contributor.author","Eisbach, Sibylle E."],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T09:24:21Z"],["dc.date.available","2018-11-07T09:24:21Z"],["dc.date.issued","2013"],["dc.description.abstract","Parkinson's disease is characterized by intracellular proteinaceous depositions known as Lewy bodies. These largely consist of the protein alpha-synuclein, whose physiological function remains unclear, but mutations and overexpression of the protein have been shown to cause early onset cases of Parkinson's disease. Deregulation of alpha-synuclein biology causes neurodegeneration and impaired neuronal trafficking, hinting at a possible contribution to the pathological mechanism. Recent studies produced some evidence hinting at the involvement of several regulators of the transport machinery such as Rab GTPases and SNARE proteins, but also shown that alpha-synuclein can be propagated between cells. Here, we discuss the molecular interplay of alpha-synuclein with the intracellular transport machinery, its consequences, and the implications for disease mechanisms."],["dc.identifier.doi","10.1007/s00109-013-1038-9"],["dc.identifier.isi","000319297200006"],["dc.identifier.pmid","23616088"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29803"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0946-2716"],["dc.title","alpha-Synuclein and intracellular trafficking: impact on the spreading of Parkinson's disease pathology"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","13"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of Pathology"],["dc.bibliographiccitation.lastpage","25"],["dc.bibliographiccitation.volume","221"],["dc.contributor.author","Miranda, Hugo Vicente"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2022-03-01T11:46:30Z"],["dc.date.available","2022-03-01T11:46:30Z"],["dc.date.issued","2009"],["dc.identifier.doi","10.1002/path.2682"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103693"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0022-3417"],["dc.title","The sour side of neurodegenerative disorders: the effects of protein glycation"],["dc.title.alternative","Effects of protein glycation in neurodegenerative disorders"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1122.e23"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Neurobiology of Aging"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Kemppainen, Susanna"],["dc.contributor.author","Rantamaki, Tomi"],["dc.contributor.author","Jeronimo-Santos, Andre"],["dc.contributor.author","Lavasseur, Gregoire"],["dc.contributor.author","Autio, Henri"],["dc.contributor.author","Karpova, Nina"],["dc.contributor.author","Karkkainen, Elisa"],["dc.contributor.author","Staven, Saara"],["dc.contributor.author","Vicente Miranda, Hugo"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Diogenes, Maria Jose"],["dc.contributor.author","Laroche, Serge"],["dc.contributor.author","Davis, Sabrina"],["dc.contributor.author","Sebastiao, Ana Maria"],["dc.contributor.author","Castren, Eero"],["dc.contributor.author","Tanila, Heikki"],["dc.date.accessioned","2018-11-07T09:10:09Z"],["dc.date.available","2018-11-07T09:10:09Z"],["dc.date.issued","2012"],["dc.description.abstract","Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity, learning, and memory. Levels of BDNF and its main receptor TrkB (TrkB.TK) have been reported to be decreased while the levels of the truncated TrkB (TrkB.T1) are increased in Alzheimer's disease. We show here that incubation with amyloid-beta increased TrkB.T1 receptor levels and decreased TrkB.TK levels in primary neurons. In vivo, APPswe/PS1dE9 transgenic mice (APdE9) showed an age-dependent relative increase in cortical but not hippocampal TrkB.T1 receptor levels compared with TrkB.TK. To investigate the role of TrkB isoforms in Alzheimer's disease, we crossed AP mice with mice overexpressing the truncated TrkB.T1 receptor (T1) or the full-length TrkB.TK isoform. Overexpression of TrkB.T1 in APdE9 mice exacerbated their spatial memory impairment while the overexpression of TrkB.TK alleviated it. These data suggest that amyloid-beta changes the ratio between TrkB isoforms in favor of the dominant-negative TrkB.T1 isoform both in vitro and in vivo and supports the role of BDNF signaling through TrkB in the pathophysiology and cognitive deficits of Alzheimer's disease. (C) 2012 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.neurobiolaging.2011.11.006"],["dc.identifier.isi","000303197100016"],["dc.identifier.pmid","22209410"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26426"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","1558-1497"],["dc.relation.issn","0197-4580"],["dc.title","Impaired TrkB receptor signaling contributes to memory impairment in APP/PS1 mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","109"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Annals of Neurology"],["dc.bibliographiccitation.lastpage","118"],["dc.bibliographiccitation.volume","74"],["dc.contributor.author","Taschenberger, G."],["dc.contributor.author","Toloe, J."],["dc.contributor.author","Tereshchenko, J."],["dc.contributor.author","Akerboom, J."],["dc.contributor.author","Wales, P."],["dc.contributor.author","Benz, R."],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Outeiro, T. F."],["dc.contributor.author","Looger, L. L."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Zweckstetter, M."],["dc.contributor.author","Kügler, Sebastian"],["dc.date.accessioned","2017-09-07T11:47:39Z"],["dc.date.available","2017-09-07T11:47:39Z"],["dc.date.issued","2013"],["dc.description.abstract","ObjectiveWhereas the contribution of -synuclein to neurodegeneration in Parkinson disease is well accepted, the putative impact of its close homologue, -synuclein, is enigmatic. -Synuclein is widely expressed throughout the central nervous system, as is -synuclein, but the physiological functions of both proteins remain unknown. Recent findings have supported the view that -synuclein can act as an ameliorating regulator of -synuclein-induced neurotoxicity, having neuroprotective rather than neurodegenerative capabilities, and being nonaggregating due to the absence of most of the aggregation-promoting NAC domain. However, a mutation of -synuclein linked to dementia with Lewy bodies rendered the protein neurotoxic in transgenic mice, and fibrillation of -synuclein has been demonstrated in vitro. MethodsNeurotoxicity and aggregation properties of -, -, and -synuclein were comparatively elucidated in the rat nigro-striatal projection and in cultured neurons. ResultsSupporting the hypothesis that -synuclein can act as a neurodegeneration-inducing factor, we demonstrated that wild-type -synuclein is neurotoxic for cultured primary neurons. Furthermore, -synuclein formed proteinase K-resistant aggregates in dopaminergic neurons in vivo, leading to pronounced and progressive neurodegeneration in rats. Expression of -synuclein caused mitochondrial fragmentation, but this fragmentation did not render mitochondria nonfunctional in terms of ion handling and respiration even at late stages of neurodegeneration. A comparison of the neurodegenerative effects induced by -, -, and -synuclein revealed that -synuclein was eventually as neurotoxic as -synuclein for nigral dopaminergic neurons, whereas -synuclein proved to be nontoxic and had very low aggregation propensity. InterpretationOur results suggest that the role of -synuclein as a putative modulator of neuropathology in aggregopathies like Parkinson disease and dementia with Lewy bodies needs to be revisited. Ann Neurol 2013;74:109-118"],["dc.identifier.doi","10.1002/ana.23905"],["dc.identifier.gro","3142329"],["dc.identifier.isi","000329198600014"],["dc.identifier.pmid","23536356"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7075"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1531-8249"],["dc.relation.issn","0364-5134"],["dc.title","β-Synuclein Aggregates and Induces Neurodegeneration in Dopaminergic Neurons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","5857"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Fonseca-Ornelas, Luis"],["dc.contributor.author","Eisbach, Sibylle E."],["dc.contributor.author","Paulat, Maria"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Fernandez, Claudio O."],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2018-11-07T09:31:47Z"],["dc.date.available","2018-11-07T09:31:47Z"],["dc.date.issued","2014"],["dc.description.abstract","alpha-synuclein is an abundant presynaptic protein that is important for regulation of synaptic vesicle trafficking, and whose misfolding plays a key role in Parkinson's disease. While alpha-synuclein is disordered in solution, it folds into a helical conformation when bound to synaptic vesicles. Stabilization of helical, folded alpha-synuclein might therefore interfere with alpha-synuclein-induced neurotoxicity. Here we show that several small molecules, which delay aggregation of alpha-synuclein in solution, including the Parkinson's disease drug selegiline, fail to interfere with misfolding of vesicle-bound alpha-synuclein. In contrast, the porphyrin phtalocyanine tetrasulfonate directly binds to vesicle-bound alpha-synuclein, stabilizes its helical conformation and thereby delays pathogenic misfolding and aggregation. Our study suggests that small-molecule-mediated stabilization of helical vesicle-bound alpha-synuclein opens new possibilities to target Parkinson's disease and related synucleinopathies."],["dc.identifier.doi","10.1038/ncomms6857"],["dc.identifier.isi","000347683000001"],["dc.identifier.pmid","25524885"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31609"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2041-1723"],["dc.title","Small molecule-mediated stabilization of vesicle-associated helical alpha-synuclein inhibits pathogenic misfolding and aggregation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","194"],["dc.bibliographiccitation.issue","3-4"],["dc.bibliographiccitation.journal","Disease Models & Mechanisms"],["dc.bibliographiccitation.lastpage","208"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Su, Linhui Julie"],["dc.contributor.author","Auluck, Pavan K."],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Yeger-Lotem, Esti"],["dc.contributor.author","Kritzer, Joshua A."],["dc.contributor.author","Tardiff, Daniel F."],["dc.contributor.author","Strathearn, Katherine E."],["dc.contributor.author","Liu, Fang"],["dc.contributor.author","Cao, Songsong"],["dc.contributor.author","Hamamichi, Shusei"],["dc.contributor.author","Lindquist, Susan"],["dc.date.accessioned","2022-03-01T11:44:04Z"],["dc.date.available","2022-03-01T11:44:04Z"],["dc.date.issued","2010"],["dc.description.abstract","SUMMARY α-Synuclein (α-syn) is a small lipid-binding protein involved in vesicle trafficking whose function is poorly characterized. It is of great interest to human biology and medicine because α-syn dysfunction is associated with several neurodegenerative disorders, including Parkinson’s disease (PD). We previously created a yeast model of α-syn pathobiology, which established vesicle trafficking as a process that is particularly sensitive to α-syn expression. We also uncovered a core group of proteins with diverse activities related to α-syn toxicity that is conserved from yeast to mammalian neurons. Here, we report that a yeast strain expressing a somewhat higher level of α-syn also exhibits strong defects in mitochondrial function. Unlike our previous strain, genetic suppression of endoplasmic reticulum (ER)-to-Golgi trafficking alone does not suppress α-syn toxicity in this strain. In an effort to identify individual compounds that could simultaneously rescue these apparently disparate pathological effects of α-syn, we screened a library of 115,000 compounds. We identified a class of small molecules that reduced α-syn toxicity at micromolar concentrations in this higher toxicity strain. These compounds reduced the formation of α-syn foci, re-established ER-to-Golgi trafficking and ameliorated α-syn-mediated damage to mitochondria. They also corrected the toxicity of α-syn in nematode neurons and in primary rat neuronal midbrain cultures. Remarkably, the compounds also protected neurons against rotenone-induced toxicity, which has been used to model the mitochondrial defects associated with PD in humans. That single compounds are capable of rescuing the diverse toxicities of α-syn in yeast and neurons suggests that they are acting on deeply rooted biological processes that connect these toxicities and have been conserved for a billion years of eukaryotic evolution. Thus, it seems possible to develop novel therapeutic strategies to simultaneously target the multiple pathological features of PD."],["dc.description.abstract","SUMMARY α-Synuclein (α-syn) is a small lipid-binding protein involved in vesicle trafficking whose function is poorly characterized. It is of great interest to human biology and medicine because α-syn dysfunction is associated with several neurodegenerative disorders, including Parkinson’s disease (PD). We previously created a yeast model of α-syn pathobiology, which established vesicle trafficking as a process that is particularly sensitive to α-syn expression. We also uncovered a core group of proteins with diverse activities related to α-syn toxicity that is conserved from yeast to mammalian neurons. Here, we report that a yeast strain expressing a somewhat higher level of α-syn also exhibits strong defects in mitochondrial function. Unlike our previous strain, genetic suppression of endoplasmic reticulum (ER)-to-Golgi trafficking alone does not suppress α-syn toxicity in this strain. In an effort to identify individual compounds that could simultaneously rescue these apparently disparate pathological effects of α-syn, we screened a library of 115,000 compounds. We identified a class of small molecules that reduced α-syn toxicity at micromolar concentrations in this higher toxicity strain. These compounds reduced the formation of α-syn foci, re-established ER-to-Golgi trafficking and ameliorated α-syn-mediated damage to mitochondria. They also corrected the toxicity of α-syn in nematode neurons and in primary rat neuronal midbrain cultures. Remarkably, the compounds also protected neurons against rotenone-induced toxicity, which has been used to model the mitochondrial defects associated with PD in humans. That single compounds are capable of rescuing the diverse toxicities of α-syn in yeast and neurons suggests that they are acting on deeply rooted biological processes that connect these toxicities and have been conserved for a billion years of eukaryotic evolution. Thus, it seems possible to develop novel therapeutic strategies to simultaneously target the multiple pathological features of PD."],["dc.identifier.doi","10.1242/dmm.004267"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/102920"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1754-8411"],["dc.relation.issn","1754-8403"],["dc.title","Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and mitochondrial dysfunction in Parkinson’s disease models"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","581"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Nature Chemical Biology"],["dc.bibliographiccitation.lastpage","582"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2022-03-01T11:45:51Z"],["dc.date.available","2022-03-01T11:45:51Z"],["dc.date.issued","2011"],["dc.identifier.doi","10.1038/nchembio.636"],["dc.identifier.pii","BFnchembio636"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103474"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1552-4469"],["dc.relation.issn","1552-4450"],["dc.title","FlAsH illuminates Aβ aggregation"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]