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","415"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Parkinson s Disease"],["dc.bibliographiccitation.lastpage","459"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Wales, Pauline"],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Lazaro, Diana F."],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T09:29:27Z"],["dc.date.available","2018-11-07T09:29:27Z"],["dc.date.issued","2013"],["dc.description.abstract","The pathogenesis of many neurodegenerative disorders arises in association with the misfolding and accumulation of a wide variety of proteins. Much emphasis has been placed on understanding the nature of these protein accumulations, including their composition, the process by which they are formed and the physiological impact they impose at cellular and, ultimately, organismal levels. Alpha-synuclein (ASYN) is the major component of protein inclusions known as Lewy bodies and Lewy neurites, which are the typical pathological hallmarks in disorders referred to as synucleinopathies. In addition, mutations or multiplications in the gene encoding for ASYN have also been shown to cause familial cases of PD, the most common synucleinopathy. Although the precise function of ASYN remains unclear, it appears to be involved in a vast array of cellular processes. Here, we review, in depth, a spectrum of cellular and molecular mechanisms that have been implicated in synucleinopathies. Importantly, detailed understanding of the biology/pathobiology of ASYN may enable the development of novel avenues for diagnosis and/or therapeutic intervention in synucleinopathies."],["dc.identifier.doi","10.3233/JPD-130216"],["dc.identifier.isi","000328332100001"],["dc.identifier.pmid","24270242"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31034"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Ios Press"],["dc.relation.issn","1877-718X"],["dc.relation.issn","1877-7171"],["dc.title","Limelight on Alpha-Synuclein: Pathological and Mechanistic Implications in Neurodegeneration"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e0190552"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PLOS ONE"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Guedes, Leonor C."],["dc.contributor.author","Soreq, Lilach"],["dc.contributor.author","Lobo, Patrícia P."],["dc.contributor.author","Mestre, Tiago"],["dc.contributor.author","Coelho, Miguel"],["dc.contributor.author","Rosa, Mário M."],["dc.contributor.author","Gonçalves, Nilza"],["dc.contributor.author","Wales, Pauline"],["dc.contributor.author","Mendes, Tiago"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2022-03-01T11:44:12Z"],["dc.date.available","2022-03-01T11:44:12Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1371/journal.pone.0190552"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/102958"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1932-6203"],["dc.relation.iserratumof","/handle/2/40290"],["dc.rights.uri","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Correction: Gene Expression Differences in Peripheral Blood of Parkinson's Disease Patients with Distinct Progression Profiles"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","erratum_ja"],["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"]]