Outeiro, Tiago Fleming

[["dc.bibliographiccitation.artnumber","107"],["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Vasili, Eftychia"],["dc.contributor.author","Dominguez-Meijide, Antonio"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2019-07-09T11:51:15Z"],["dc.date.available","2019-07-09T11:51:15Z"],["dc.date.issued","2019"],["dc.description.abstract","Alzheimer's disease (AD) and Parkinson's disease (PD) are age-associated neurodegenerative disorders characterized by the misfolding and aggregation of alpha-synuclein (aSyn) and tau, respectively. The coexistence of aSyn and tau aggregates suggests a strong overlap between tauopathies and synucleinopathies. Interestingly, misfolded forms of aSyn and tau can propagate from cell to cell, and throughout the brain, thereby templating the misfolding of native forms of the proteins. The exact mechanisms involved in the propagation of the two proteins show similarities, and are reminiscent of the spreading characteristic of prion diseases. Recently, several models were developed to study the spreading of aSyn and tau. Here, we discuss the mechanisms involved, the similarities and differences between the spreading of the two proteins and that of the prion protein, and the different cell and animal models used for studying these processes. Ultimately, a deeper understanding of the molecular mechanisms involved may lead to the identification of novel targets for therapeutic intervention in a variety of devastating neurodegenerative diseases."],["dc.identifier.doi","10.3389/fnmol.2019.00107"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16088"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59910"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation","info:eu-repo/grantAgreement/EC/H2020/116060/EU//IMPRiND"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","573"],["dc.subject.ddc","612"],["dc.title","Spreading of α-Synuclein and Tau: A Systematic Comparison of the Mechanisms Involved"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","5"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurodegeneration"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Koss, David J."],["dc.contributor.author","Erskine, Daniel"],["dc.contributor.author","Walker, Lauren"],["dc.contributor.author","Kurzawa-Akanbi, Marzena"],["dc.contributor.author","Burn, David"],["dc.contributor.author","Donaghy, Paul"],["dc.contributor.author","Morris, Christopher"],["dc.contributor.author","Taylor, John-Paul"],["dc.contributor.author","Thomas, Alan"],["dc.contributor.author","Attems, Johannes"],["dc.contributor.author","McKeith, Ian"],["dc.date.accessioned","2019-07-09T11:51:10Z"],["dc.date.available","2019-07-09T11:51:10Z"],["dc.date.issued","2019"],["dc.description.abstract","Dementia with Lewy bodies (DLB) is an age-associated neurodegenerative disorder producing progressive cognitive decline that interferes with normal life and daily activities. Neuropathologically, DLB is characterised by the accumulation of aggregated α-synuclein protein in Lewy bodies and Lewy neurites, similar to Parkinson's disease (PD). Extrapyramidal motor features characteristic of PD, are common in DLB patients, but are not essential for the clinical diagnosis of DLB. Since many PD patients develop dementia as disease progresses, there has been controversy about the separation of DLB from PD dementia (PDD) and consensus reports have put forward guidelines to assist clinicians in the identification and management of both syndromes. Here, we present basic concepts and definitions, based on our current understanding, that should guide the community to address open questions that will, hopefully, lead us towards improved diagnosis and novel therapeutic strategies for DLB and other synucleinopathies."],["dc.identifier.doi","10.1186/s13024-019-0306-8"],["dc.identifier.pmid","30665447"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16061"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59887"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","006"],["dc.subject.ddc","573"],["dc.subject.ddc","612"],["dc.title","Dementia with Lewy bodies: an update and outlook"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","13713"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific reports"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Vicente Miranda, Hugo"],["dc.contributor.author","Cássio, Rafaela"],["dc.contributor.author","Correia-Guedes, Leonor"],["dc.contributor.author","Gomes, Marcos António"],["dc.contributor.author","Chegão, Ana"],["dc.contributor.author","Miranda, Elisa"],["dc.contributor.author","Soares, Tiago"],["dc.contributor.author","Coelho, Miguel"],["dc.contributor.author","Rosa, Mário Miguel"],["dc.contributor.author","Ferreira, Joaquim J"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2019-07-09T11:44:39Z"],["dc.date.available","2019-07-09T11:44:39Z"],["dc.date.issued","2017-10-20"],["dc.description.abstract","Parkinson's disease (PD) is a progressive neurodegenerative disorder known for the typical motor features associated. Pathologically, it is characterized by the intracellular accumulation of alpha-synuclein (aSyn) in Lewy bodies and Lewy neurites. Currently, there are no established biochemical markers for diagnosing or for following disease progression, a major limitation for the clinical practice. Posttranslational modifications (PTMs) in aSyn have been identified and implicated on its pathobiology. Since aSyn is abundant in blood erythrocytes, we aimed to evaluate whether PTMs of aSyn in the blood might hold value as a biomarker for PD. We examined 58 patients with PD and 30 healthy age-matched individuals. We found that the levels of Y125 phosphorylated, Y39 nitrated, and glycated aSyn were increased in PD, while those of SUMO were reduced. A combinatory analysis of the levels of these PTMs resulted in an increased sensitivity, with an area under curve (AUC) of 0.843 for PD versus healthy controls, and correlated with disease severity and duration. We conclude that the levels of these selected PTMs hold strong potential as biochemical markers for PD. Ultimately, our findings might facilitate the monitoring of disease progression in clinical trials, opening the possibility for developing more effective therapies against PD."],["dc.identifier.doi","10.1038/s41598-017-14175-5"],["dc.identifier.pmid","29057912"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14852"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59058"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","573"],["dc.subject.ddc","612"],["dc.title","Posttranslational modifications of blood-derived alpha-synuclein as biochemical markers for Parkinson's disease."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Aging Cell"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Sampaio‐Marques, Belém"],["dc.contributor.author","Guedes, Ana"],["dc.contributor.author","Vasilevskiy, Igor"],["dc.contributor.author","Gonçalves, Susana"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Winderickx, Joris"],["dc.contributor.author","Burhans, William C."],["dc.contributor.author","Ludovico, Paula"],["dc.date.accessioned","2019-11-27T10:13:28Z"],["dc.date.accessioned","2021-10-27T13:21:36Z"],["dc.date.available","2019-11-27T10:13:28Z"],["dc.date.available","2021-10-27T13:21:36Z"],["dc.date.issued","2019"],["dc.description.abstract","ƒ¿ ]Synuclein (aSyn) toxicity is associated with cell cycle alterations, activation of DNA damage responses (DDR), and deregulation of autophagy. However, the relationships between these phenomena remain largely unknown. Here, we demonstrate that in a yeast model of aSyn toxicity and aging, aSyn expression induces Ras2 ]dependent growth signaling, cell cycle re ]entry, DDR activation, autophagy, and autophagic degradation of ribonucleotide reductase 1 (Rnr1), a protein required for the activity of ribonucleotide reductase and dNTP synthesis. These events lead to cell death and aging, which are abrogated by deleting RAS2, inhibiting DDR or autophagy, or overexpressing RNR1. aSyn expression in human H4 neuroglioma cells also induces cell cycle re ]entry and S ]phase arrest, autophagy, and degradation of RRM1, the human homologue of RNR1, and inhibiting autophagic degradation of RRM1 rescues cells from cell death. Our findings represent a model for aSyn toxicity that has important implications for understanding synucleinopathies and other age ]related neurodegenerative diseases."],["dc.identifier.doi","10.1111/acel.12922"],["dc.identifier.eissn","1474-9726"],["dc.identifier.issn","1474-9718"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16742"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92034"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","1474-9726"],["dc.relation.issn","1474-9718"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","573"],["dc.subject.ddc","612"],["dc.title","α‐Synuclein toxicity in yeast and human cells is caused by cell cycle re‐entry and autophagy degradation of ribonucleotide reductase 1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]