Pinho, Raquel

[["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"]]

[["dc.bibliographiccitation.firstpage","E6506"],["dc.bibliographiccitation.issue","42"],["dc.bibliographiccitation.journal","PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"],["dc.bibliographiccitation.lastpage","E6515"],["dc.bibliographiccitation.volume","113"],["dc.contributor.author","Villar-Pique, Anna"],["dc.contributor.author","da Fonseca, Tomas Lopes"],["dc.contributor.author","Sant'Anna, Ricardo"],["dc.contributor.author","Szegoe, Eva Monika"],["dc.contributor.author","Fonseca-Ornelas, Luis"],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Carija, Anita"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Masaracchia, Caterina"],["dc.contributor.author","Gonzalez, Enrique Abad"],["dc.contributor.author","Rossetti, Giulia"],["dc.contributor.author","Carloni, Paolo"],["dc.contributor.author","Fernandez, Claudio O."],["dc.contributor.author","Foguel, Debora"],["dc.contributor.author","Milosevic, Ira"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Ventura, Salvador"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T10:06:57Z"],["dc.date.available","2018-11-07T10:06:57Z"],["dc.date.issued","2016"],["dc.description.abstract","Synucleinopathies are a group of progressive disorders characterized by the abnormal aggregation and accumulation of alpha-synuclein (aSyn), an abundant neuronal protein that can adopt different conformations and biological properties. Recently, aSyn pathology was shown to spread between neurons in a prion-like manner. Proteins like aSyn that exhibit self-propagating capacity appear to be able to adopt different stable conformational states, known as protein strains, which can be modulated both by environmental and by protein-intrinsic factors. Here, we analyzed these factors and found that the unique combination of the neurodegeneration-related metal copper and the pathological H50Q aSyn mutation induces a significant alteration in the aggregation properties of aSyn. We compared the aggregation of WT and H50Q aSyn with and without copper, and assessed the effects of the resultant protein species when applied to primary neuronal cultures. The presence of copper induces the formation of structurally different and less-damaging aSyn aggregates. Interestingly, these aggregates exhibit a stronger capacity to induce aSyn inclusion formation in recipient cells, which demonstrates that the structural features of aSyn species determine their effect in neuronal cells and supports a lack of correlation between toxicity and inclusion formation. In total, our study provides strong support in favor of the hypothesis that protein aggregation is not a primary cause of cytotoxicity."],["dc.identifier.doi","10.1073/pnas.1606791113"],["dc.identifier.isi","000385610400024"],["dc.identifier.pmid","27708160"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39195"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Environmental and genetic factors support the dissociation between alpha-synuclein aggregation and toxicity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e2000374"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","PLoS Biology"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","de Oliveira, Rita Machado"],["dc.contributor.author","Miranda, Hugo Vicente"],["dc.contributor.author","Francelle, Laetitia"],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Szegoe, Eva Monika"],["dc.contributor.author","Martinho, Renato"],["dc.contributor.author","Munari, Francesca"],["dc.contributor.author","Lazaro, Diana F."],["dc.contributor.author","Moniot, Sebastien"],["dc.contributor.author","Guerreiro, Patricia S."],["dc.contributor.author","Fonseca, Luis"],["dc.contributor.author","Marijanovic, Zrinka"],["dc.contributor.author","Antas, Pedro"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Enguita, Francisco Javier"],["dc.contributor.author","Fauvet, Bruno"],["dc.contributor.author","Penque, Deborah"],["dc.contributor.author","Pais, Teresa Faria"],["dc.contributor.author","Tong, Qiang"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Kuegler, Sebastian"],["dc.contributor.author","Lashuel, Hilal Ahmed"],["dc.contributor.author","Steegborn, Clemens"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T10:26:48Z"],["dc.date.available","2018-11-07T10:26:48Z"],["dc.date.issued","2017"],["dc.description.abstract","Sirtuin genes have been associated with aging and are known to affect multiple cellular pathways. Sirtuin 2 was previously shown to modulate proteotoxicity associated with ageassociated neurodegenerative disorders such as Alzheimer and Parkinson disease (PD). However, the precise molecular mechanisms involved remain unclear. Here, we provide mechanistic insight into the interplay between sirtuin 2 and alpha-synuclein, the major component of the pathognomonic protein inclusions in PD and other synucleinopathies. We found that alpha-synuclein is acetylated on lysines 6 and 10 and that these residues are deacetylated by sirtuin 2. Genetic manipulation of sirtuin 2 levels in vitro and in vivo modulates the levels of alpha-synuclein acetylation, its aggregation, and autophagy. Strikingly, mutants blocking acetylation exacerbate alpha-synuclein toxicity in vivo, in the substantia nigra of rats. Our study identifies alpha-synuclein acetylation as a key regulatory mechanism governing alpha-synuclein aggregation and toxicity, demonstrating the potential therapeutic value of sirtuin 2 inhibition in synucleinopathies."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1371/journal.pbio.2000374"],["dc.identifier.isi","000397909600002"],["dc.identifier.pmid","28257421"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14377"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43121"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Public Library Science"],["dc.relation.haserratum","/handle/2/102935"],["dc.relation.issn","1545-7885"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The mechanism of sirtuin 2-mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease"],["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.firstpage","2231"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","2246"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Paiva, Isabel"],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Pavlou, Maria Angeliki"],["dc.contributor.author","Hennion, Magali"],["dc.contributor.author","Wales, Pauline"],["dc.contributor.author","Schütz, Anna-Lena"],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Szegő, Éva M."],["dc.contributor.author","Kerimoglu, Cemil"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Rego, Ana Cristina"],["dc.contributor.author","Fischer, André"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Outeiro, Tiago F."],["dc.date.accessioned","2018-04-23T11:47:17Z"],["dc.date.available","2018-04-23T11:47:17Z"],["dc.date.issued","2017"],["dc.description.abstract","Alpha-synuclein (aSyn) is considered a major culprit in Parkinson’s disease (PD) pathophysiology. However, the precise molecular function of the protein remains elusive. Recent evidence suggests that aSyn may play a role on transcription regulation, possibly by modulating the acetylation status of histones. Our study aimed at evaluating the impact of wild-type (WT) and mutant A30P aSyn on gene expression, in a dopaminergic neuronal cell model, and decipher potential mechanisms underlying aSyn-mediated transcriptional deregulation. We performed gene expression analysis using RNA-sequencing in Lund Human Mesencephalic (LUHMES) cells expressing endogenous (control) or increased levels of WT or A30P aSyn. Compared to control cells, cells expressing both aSyn variants exhibited robust changes in the expression of several genes, including downregulation of major genes involved in DNA repair. WT aSyn, unlike A30P aSyn, promoted DNA damage and increased levels of phosphorylated p53. In dopaminergic neuronal cells, increased aSyn expression led to reduced levels of acetylated histone 3. Importantly, treatment with sodium butyrate, a histone deacetylase inhibitor (HDACi), rescued WT aSyn-induced DNA damage, possibly via upregulation of genes involved in DNA repair. Overall, our findings provide novel and compelling insight into the mechanisms associated with aSyn neurotoxicity in dopaminergic cells, which could be ameliorated with an HDACi. Future studies will be crucial to further validate these findings and to define novel possible targets for intervention in PD."],["dc.identifier.doi","10.1093/hmg/ddx114"],["dc.identifier.gro","3142201"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13321"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0964-6906"],["dc.title","Sodium butyrate rescues dopaminergic cells from alpha-synuclein-induced transcriptional deregulation and DNA damage"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]