Outeiro, Tiago Fleming

[["dc.bibliographiccitation.firstpage","1539"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Cellular and Molecular Neurobiology"],["dc.bibliographiccitation.lastpage","1550"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Gustafsson, Gabriel"],["dc.contributor.author","Lööv, Camilla"],["dc.contributor.author","Persson, Emma"],["dc.contributor.author","Lázaro, Diana F."],["dc.contributor.author","Takeda, Shuko"],["dc.contributor.author","Bergström, Joakim"],["dc.contributor.author","Erlandsson, Anna"],["dc.contributor.author","Sehlin, Dag"],["dc.contributor.author","Balaj, Leonora"],["dc.contributor.author","György, Bence"],["dc.contributor.author","Hallbeck, Martin"],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Breakefield, Xandra O."],["dc.contributor.author","Hyman, Bradley T."],["dc.contributor.author","Ingelsson, Martin"],["dc.date.accessioned","2020-12-10T14:11:26Z"],["dc.date.available","2020-12-10T14:11:26Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1007/s10571-018-0622-5"],["dc.identifier.eissn","1573-6830"],["dc.identifier.issn","0272-4340"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15557"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71076"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Secretion and Uptake of α-Synuclein Via Extracellular Vesicles in Cultured Cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","889"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","890"],["dc.bibliographiccitation.volume","157"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2021-04-14T08:28:16Z"],["dc.date.available","2021-04-14T08:28:16Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract image"],["dc.description.abstract","The process of a‐syn aggregation is thought to be central in synucleinopathies, but has been difficult to study in the laboratory. Different models attempt to recapitulate specific aspects of the aggregation process. The BiFC assay uses engineered fusion proteins in order to enable the detection of a‐syn dimers and oligomers in living cells. As any model, it has strengths and limitations and, therefore, should only be regarded as a model for the study of basic molecular mechanisms involved in PD and other synucleinopathies. image"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.identifier.doi","10.1111/jnc.15264"],["dc.identifier.pmid","33300125"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82557"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/100"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1471-4159"],["dc.relation.issn","0022-3042"],["dc.relation.workinggroup","RG Outeiro (Experimental Neurodegeneration)"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes."],["dc.title","Alpha‐synuclein oligomerization and aggregation: A model will always be a model"],["dc.title.alternative","This is a response to “Monitoring alpha‐synuclein oligomerization and aggregation using bimolecular fluorescence complementation assays: What you see is not always what you get”. Read the reply on “Alpha‐Synuclein oligomerization and aggregation: All models are useful but only if we know what they model”. The articles are accompanied by a Preface “How good are cellular models?”."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5724"],["dc.bibliographiccitation.issue","16"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Morato Torres, C. Alejandra"],["dc.contributor.author","Wassouf, Zinah"],["dc.contributor.author","Zafar, Faria"],["dc.contributor.author","Sastre, Danuta"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Schüle, Birgitt"],["dc.date.accessioned","2021-04-14T08:23:46Z"],["dc.date.available","2021-04-14T08:23:46Z"],["dc.date.issued","2020"],["dc.description.abstract","Neurodevelopmental and late-onset neurodegenerative disorders present as separate entities that are clinically and neuropathologically quite distinct. However, recent evidence has highlighted surprising commonalities and converging features at the clinical, genomic, and molecular level between these two disease spectra. This is particularly striking in the context of autism spectrum disorder (ASD) and Parkinson’s disease (PD). Genetic causes and risk factors play a central role in disease pathophysiology and enable the identification of overlapping mechanisms and pathways. Here, we focus on clinico-genetic studies of causal variants and overlapping clinical and cellular features of ASD and PD. Several genes and genomic regions were selected for our review, including SNCA (alpha-synuclein), PARK2 (parkin RBR E3 ubiquitin protein ligase), chromosome 22q11 deletion/DiGeorge region, and FMR1 (fragile X mental retardation 1) repeat expansion, which influence the development of both ASD and PD, with converging features related to synaptic function and neurogenesis. Both PD and ASD display alterations and impairments at the synaptic level, representing early and key disease phenotypes, which support the hypothesis of converging mechanisms between the two types of diseases. Therefore, understanding the underlying molecular mechanisms might inform on common targets and therapeutic approaches. We propose to re-conceptualize how we understand these disorders and provide a new angle into disease targets and mechanisms linking neurodevelopmental disorders and neurodegeneration."],["dc.identifier.doi","10.3390/ijms21165724"],["dc.identifier.pmid","32785033"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81042"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/163"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/98"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["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.eissn","1422-0067"],["dc.relation.workinggroup","RG Outeiro (Experimental Neurodegeneration)"],["dc.rights","CC BY 4.0"],["dc.title","The Role of Alpha-Synuclein and Other Parkinson’s Genes in Neurodevelopmental and Neurodegenerative Disorders"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","overview_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Molecular Neurobiology"],["dc.contributor.author","Vasili, Eftychia"],["dc.contributor.author","Dominguez-Meijide, Antonio"],["dc.contributor.author","Flores-León, Manuel"],["dc.contributor.author","Al-Azzani, Mohammed"],["dc.contributor.author","Kanellidi, Angeliki"],["dc.contributor.author","Melki, Ronald"],["dc.contributor.author","Stefanis, Leonidas"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2022-02-01T10:31:58Z"],["dc.date.available","2022-02-01T10:31:58Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract Parkinson’s disease is a progressive neurodegenerative disorder characterized by the accumulation of misfolded alpha-synuclein in intraneuronal inclusions known as Lewy bodies and Lewy neurites. Multiple studies strongly implicate the levels of alpha-synuclein as a major risk factor for the onset and progression of Parkinson’s disease. Alpha-synuclein pathology spreads progressively throughout interconnected brain regions but the precise molecular mechanisms underlying the seeding of alpha-synuclein aggregation are still unclear. Here, using stable cell lines expressing alpha-synuclein, we examined the correlation between endogenous alpha-synuclein levels and the seeding propensity by exogenous alpha-synuclein preformed fibrils. We applied biochemical approaches and imaging methods in stable cell lines expressing alpha-synuclein and in primary neurons to determine the impact of alpha-synuclein levels on seeding and aggregation. Our results indicate that the levels of alpha-synuclein define the pattern and severity of aggregation and the extent of p-alpha-synuclein deposition, likely explaining the selective vulnerability of different cell types in synucleinopathies. The elucidation of the cellular processes involved in the pathological aggregation of alpha-synuclein will enable the identification of novel targets and the development of therapeutic strategies for Parkinson’s disease and other synucleinopathies."],["dc.identifier.doi","10.1007/s12035-021-02713-2"],["dc.identifier.pii","2713"],["dc.identifier.pmid","34984585"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/98991"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/440"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-517"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1559-1182"],["dc.relation.issn","0893-7648"],["dc.relation.workinggroup","RG Outeiro (Experimental Neurodegeneration)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Endogenous Levels of Alpha-Synuclein Modulate Seeding and Aggregation in Cultured Cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","344"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.lastpage","352"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Donmez, Gizem"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T09:27:36Z"],["dc.date.available","2018-11-07T09:27:36Z"],["dc.date.issued","2013"],["dc.description.abstract","Sirtuins are NAD-dependent protein deacetylases known to have protective effects against age-related diseases such as cancer, diabetes, cardiovascular and neurodegenerative diseases. In mammals, there are seven sirtuins (SIRT1-7), which display diversity in subcellular localization and function. While SIRT1 has been extensively investigated due to its initial connection with lifespan extension and involvement in calorie restriction, important biological and therapeutic roles of other sirtuins have only recently been recognized. Here, we review the potential roles and effects of SIRT1 and SIRT2 in neurodegenerative diseases. We discuss different functions and targets of SIRT1 and SIRT2 in a variety of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD) and Huntington's Disease (HD). We also cover the role of SIRT1 in neuronal differentiation due to the possible implications in neurodegenerative conditions, and conclude with an outlook on the potential therapeutic value of SIRT1 and SIRT2 in these disorders."],["dc.identifier.doi","10.1002/emmm.201302451"],["dc.identifier.isi","000315861200004"],["dc.identifier.pmid","23417962"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10684"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30576"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1757-4676"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","SIRT1 and SIRT2: emerging targets in neurodegeneration"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Molecular Neuroscience"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Popova, Blagovesta"],["dc.contributor.author","Wang, Dan"],["dc.contributor.author","Rajavel, Abirami"],["dc.contributor.author","Dhamotharan, Karthikeyan"],["dc.contributor.author","Lázaro, Diana F."],["dc.contributor.author","Gerke, Jennifer"],["dc.contributor.author","Uhrig, Joachim F."],["dc.contributor.author","Hoppert, Michael"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Braus, Gerhard H."],["dc.date.accessioned","2021-06-01T09:42:26Z"],["dc.date.available","2021-06-01T09:42:26Z"],["dc.date.issued","2021"],["dc.description.abstract","Aggregation of α-synuclein (αSyn) into proteinaceous deposits is a pathological hallmark of a range of neurodegenerative diseases including Parkinson’s disease (PD). Numerous lines of evidence indicate that the accumulation of toxic oligomeric and prefibrillar αSyn species may underpin the cellular toxicity and spread of pathology between cells. Therefore, aggregation of αSyn is considered a priority target for drug development, as aggregation inhibitors are expected to reduce αSyn toxicity and serve as therapeutic agents. Here, we used the budding yeast S. cerevisiae as a platform for the identification of short peptides that inhibit αSyn aggregation and toxicity. A library consisting of approximately one million peptide variants was utilized in two high-throughput screening approaches for isolation of library representatives that reduce αSyn-associated toxicity and aggregation. Seven peptides were isolated that were able to suppress specifically αSyn toxicity and aggregation in living cells. Expression of the peptides in yeast reduced the accumulation of αSyn-induced reactive oxygen species and increased cell viability. Next, the peptides were chemically synthesized and probed for their ability to modulate αSyn aggregation in vitro . Two synthetic peptides, K84s and K102s, of 25 and 19 amino acids, respectively, significantly inhibited αSyn oligomerization and aggregation at sub-stoichiometric molar ratios. Importantly, K84s reduced αSyn aggregation in human cells. These peptides represent promising αSyn aggregation antagonists for the development of future therapeutic interventions."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.3389/fnmol.2021.659926"],["dc.identifier.pmid","33912013"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17845"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85254"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/420"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.intern","Merged from goescholar"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1662-5099"],["dc.relation.workinggroup","RG Outeiro (Experimental Neurodegeneration)"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Identification of Two Novel Peptides That Inhibit α-Synuclein Toxicity and Aggregation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1876"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Molecular Psychiatry"],["dc.bibliographiccitation.lastpage","1900"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Temido-Ferreira, Mariana"],["dc.contributor.author","Ferreira, Diana G."],["dc.contributor.author","Batalha, Vânia L."],["dc.contributor.author","Marques-Morgado, Inês"],["dc.contributor.author","Coelho, Joana E."],["dc.contributor.author","Pereira, Pedro"],["dc.contributor.author","Gomes, Rui"],["dc.contributor.author","Pinto, Andreia"],["dc.contributor.author","Carvalho, Sara"],["dc.contributor.author","Canas, Paula M."],["dc.contributor.author","Cuvelier, Laetitia"],["dc.contributor.author","Buée-Scherrer, Valerie"],["dc.contributor.author","Faivre, Emilie"],["dc.contributor.author","Baqi, Younis"],["dc.contributor.author","Müller, Christa E."],["dc.contributor.author","Pimentel, José"],["dc.contributor.author","Schiffmann, Serge N."],["dc.contributor.author","Buée, Luc"],["dc.contributor.author","Bader, Michael"],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Blum, David"],["dc.contributor.author","Cunha, Rodrigo A."],["dc.contributor.author","Marie, Hélène"],["dc.contributor.author","Pousinha, Paula A."],["dc.contributor.author","Lopes, Luísa V."],["dc.date.accessioned","2021-04-14T08:24:30Z"],["dc.date.available","2021-04-14T08:24:30Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1038/s41380-018-0110-9"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15577"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81305"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1476-5578"],["dc.relation.issn","1359-4184"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Age-related shift in LTD is dependent on neuronal adenosine A2A receptors interplay with mGluR5 and NMDA receptors"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","71"],["dc.bibliographiccitation.journal","Frontiers in Pharmacology"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Kazantsev, Aleksey G."],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2019-07-09T11:55:01Z"],["dc.date.available","2019-07-09T11:55:01Z"],["dc.date.issued","2012-04-24"],["dc.description.abstract","The sirtuin family of NAD+-dependent enzymes has received much of attention in recent years due to their diverse physiological functions in metabolism, aging, and age-related human diseases. The mammalian sirtuins (SIRT1-7) act as NAD+-dependent protein deacetylases and weak mono-ADP-ribosyl transferases on a variety of targets, including histones, transcription factors, and apoptotic modulators. The sirtuins appear to be the key sensors for available energy stores, which function as molecular switch between protein acetylation and metabolism. Furthermore, it has been shown in a broad range of experimental disease models, from yeast to mouse models, that modulation of sirtuin activities, particularly that of the most studied SIRT1 protein, suppresses or ameliorates pathological states, and thus sirtuins constitute attractive novel therapeutic targets for many age-related disorders, for most metabolic disorders such as diabetes and obesity."],["dc.identifier.doi","10.3389/fphar.2012.00071"],["dc.identifier.fs","593034"],["dc.identifier.pmid","22536186"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9980"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60781"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1663-9812"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Editorial on Special Topic: Sirtuins in Metabolism, Aging, and Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","editorial_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1994"],["dc.bibliographiccitation.journal","Cell Death and Disease"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Oliveira, Luis M. A."],["dc.contributor.author","Falomir-Lockhart, Lisandro J."],["dc.contributor.author","Botelho, Michelle Gralle"],["dc.contributor.author","Lin, K-H"],["dc.contributor.author","Wales, Pauline"],["dc.contributor.author","Koch, Jan Christoph"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Taschenberger, Holger"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Schuele, B."],["dc.contributor.author","Arndt-Jovin, Donna J."],["dc.contributor.author","Jovin, Thomas M."],["dc.date.accessioned","2018-11-07T09:49:15Z"],["dc.date.available","2018-11-07T09:49:15Z"],["dc.date.issued","2015"],["dc.description.abstract","We have assessed the impact of alpha-synuclein overexpression on the differentiation potential and phenotypic signatures of two neural-committed induced pluripotent stem cell lines derived from a Parkinson's disease patient with a triplication of the human SNCA genomic locus. In parallel, comparative studies were performed on two control lines derived from healthy individuals and lines generated from the patient iPS-derived neuroprogenitor lines infected with a lentivirus incorporating a small hairpin RNA to knock down the SNCA mRNA. The SNCA triplication lines exhibited a reduced capacity to differentiate into dopaminergic or GABAergic neurons and decreased neurite outgrowth and lower neuronal activity compared with control cultures. This delayed maturation phenotype was confirmed by gene expression profiling, which revealed a significant reduction in mRNA for genes implicated in neuronal differentiation such as delta-like homolog 1 (DLK1), gamma-aminobutyric acid type B receptor subunit 2 (GABABR2), nuclear receptor related 1 protein (NURR1), G-protein-regulated inward-rectifier potassium channel 2 (GIRK-2) and tyrosine hydroxylase (TH). The differentiated patient cells also demonstrated increased autophagic flux when stressed with chloroquine. We conclude that a two-fold overexpression of alpha-synuclein caused by a triplication of the SNCA gene is sufficient to impair the differentiation of neuronal progenitor cells, a finding with implications for adult neurogenesis and Parkinson's disease progression, particularly in the context of bioenergetic dysfunction."],["dc.identifier.doi","10.1038/cddis.2015.318"],["dc.identifier.isi","000367155300027"],["dc.identifier.pmid","26610207"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12755"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35470"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2041-4889"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Elevated alpha-synuclein caused by SNCA gene triplication impairs neuronal differentiation and maturation in Parkinson's patient-derived induced pluripotent stem cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e0157852"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Guedes, Leonor C."],["dc.contributor.author","Soreq, Lilach"],["dc.contributor.author","Lobo, Patricia P."],["dc.contributor.author","Mestre, Tiago"],["dc.contributor.author","Coelho, Miguel"],["dc.contributor.author","Rosa, Mario M."],["dc.contributor.author","Goncalves, Nilza"],["dc.contributor.author","Wales, Pauline"],["dc.contributor.author","Mendes, Tiago"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Fahlbusch, Christiane"],["dc.contributor.author","Bonifati, Vincenzo"],["dc.contributor.author","Bonin, Michael"],["dc.contributor.author","Miltenberger-Miltenyi, Gabriel"],["dc.contributor.author","Borovecki, Fran"],["dc.contributor.author","Soreq, Hermona"],["dc.contributor.author","Ferreira, Joaquim J."],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T10:12:42Z"],["dc.date.available","2018-11-07T10:12:42Z"],["dc.date.issued","2016"],["dc.description.abstract","The prognosis of neurodegenerative disorders is clinically challenging due to the inexistence of established biomarkers for predicting disease progression. Here, we performed an exploratory cross-sectional, case-control study aimed at determining whether gene expression differences in peripheral blood may be used as a signature of Parkinson's disease (PD) progression, thereby shedding light into potential molecular mechanisms underlying disease development. We compared transcriptional profiles in the blood from 34 PD patients who developed postural instability within ten years with those of 33 patients who did not develop postural instability within this time frame. Our study identified >200 differentially expressed genes between the two groups. The expression of several of the genes identified was previously found deregulated in animal models of PD and in PD patients. Relevant genes were selected for validation by real-time PCR in a subset of patients. The genes validated were linked to nucleic acid metabolism, mitochondria, immune response and intracellular-transport. Interestingly, we also found deregulation of these genes in a dopaminergic cell model of PD, a simple paradigm that can now be used to further dissect the role of these molecular players on dopaminergic cell loss. Altogether, our study provides preliminary evidence that expression changes in specific groups of genes and pathways, detected in peripheral blood samples, may be correlated with differential PD progression. Our exploratory study suggests that peripheral gene expression profiling may prove valuable for assisting in prediction of PD prognosis, and identifies novel culprits possibly involved in dopaminergic cell death. Given the exploratory nature of our study, further investigations using independent, well-characterized cohorts will be essential in order to validate our candidates as predictors of PD prognosis and to definitively confirm the value of gene expression analysis in aiding patient stratification and therapeutic intervention."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.identifier.doi","10.1371/journal.pone.0157852"],["dc.identifier.isi","000378212000048"],["dc.identifier.pmid","27322389"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13385"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40290"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.haserratum","/handle/2/102958"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]