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","878"],["dc.bibliographiccitation.journal","Brain"],["dc.bibliographiccitation.lastpage","886"],["dc.bibliographiccitation.volume","140"],["dc.contributor.author","Pavlou, Maria Angeliki S."],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Paiva, Isabel"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T10:25:54Z"],["dc.date.available","2018-11-07T10:25:54Z"],["dc.date.issued","2017"],["dc.description.abstract","Parkinson's disease is the second most prevalent neurodegenerative disorder. The main neuropathological hallmarks of the disease are the degeneration of dopaminergic neurons in the substantia nigra pars compacta and the accumulation of protein inclusions known as Lewy bodies. Recently, great attention has been given to the study of genes associated with both familial and sporadic forms of Parkinson's disease. Among them, the alpha-synuclein gene is believed to play a central role in the disease and is, therefore, one of the most studied genes. Parkinson's disease is a complex disorder and, as such, derives from the interaction between genetic and environmental factors. Here, we offer an update on the landscape of epigenetic-mediated regulation of gene expression that has been linked with alpha-synuclein and associated with Parkinson's disease. We also provide an overview of how epigenetic modifications can influence the transcription and/or translation of the alpha-synuclein gene and, on the other hand, how a-synuclein function/dysfunction can, per se, affect the epigenetic landscape. Finally, we discuss how a deeper understanding of the epigenetic profile of alpha-synuclein may enable the development of novel therapeutic approaches for Parkinson's disease and other synucleinopathies."],["dc.identifier.doi","10.1093/brain/aww227"],["dc.identifier.isi","000397319400013"],["dc.identifier.pmid","27585855"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42946"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1460-2156"],["dc.relation.issn","0006-8950"],["dc.title","The yin and yang of alpha-synuclein-associated epigenetics in Parkinson's disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e1006098"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","PLOS Genetics"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Kleinknecht, Alexandra"],["dc.contributor.author","Popova, Blagovesta"],["dc.contributor.author","Lázaro, Diana F."],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Valerius, Oliver"],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Braus, Gerhard H."],["dc.contributor.editor","Lu, Bingwei"],["dc.date.accessioned","2018-09-28T07:41:43Z"],["dc.date.available","2018-09-28T07:41:43Z"],["dc.date.issued","2016"],["dc.description.abstract","Parkinson´s disease (PD) is characterized by the presence of proteinaceous inclusions called Lewy bodies that are mainly composed of α-synuclein (αSyn). Elevated levels of oxidative or nitrative stresses have been implicated in αSyn related toxicity. Phosphorylation of αSyn on serine 129 (S129) modulates autophagic clearance of inclusions and is prominently found in Lewy bodies. The neighboring tyrosine residues Y125, Y133 and Y136 are phosphorylation and nitration sites. Using a yeast model of PD, we found that Y133 is required for protective S129 phosphorylation and for S129-independent proteasome clearance. αSyn can be nitrated and form stable covalent dimers originating from covalent crosslinking of two tyrosine residues. Nitrated tyrosine residues, but not di-tyrosine-crosslinked dimers, contributed to αSyn cytotoxicity and aggregation. Analysis of tyrosine residues involved in nitration and crosslinking revealed that the C-terminus, rather than the N-terminus of αSyn, is modified by nitration and di-tyrosine formation. The nitration level of wild-type αSyn was higher compared to that of A30P mutant that is non-toxic in yeast. A30P formed more dimers than wild-type αSyn, suggesting that dimer formation represents a cellular detoxification pathway in yeast. Deletion of the yeast flavohemoglobin gene YHB1 resulted in an increase of cellular nitrative stress and cytotoxicity leading to enhanced aggregation of A30P αSyn. Yhb1 protected yeast from A30P-induced mitochondrial fragmentation and peroxynitrite-induced nitrative stress. Strikingly, overexpression of neuroglobin, the human homolog of YHB1, protected against αSyn inclusion formation in mammalian cells. In total, our data suggest that C-terminal Y133 plays a major role in αSyn aggregate clearance by supporting the protective S129 phosphorylation for autophagy and by promoting proteasome clearance. C-terminal tyrosine nitration increases pathogenicity and can only be partially detoxified by αSyn di-tyrosine dimers. Our findings uncover a complex interplay between S129 phosphorylation and C-terminal tyrosine modifications of αSyn that likely participates in PD pathology."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2016"],["dc.identifier.doi","10.1371/journal.pgen.1006098"],["dc.identifier.pmid","27341336"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13384"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15831"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","1553-7404"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","C-Terminal Tyrosine Residue Modifications Modulate the Protective Phosphorylation of Serine 129 of α-Synuclein in a Yeast Model of Parkinson's Disease"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["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","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","496"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","The World Journal of Biological Psychiatry"],["dc.bibliographiccitation.lastpage","504"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Wang, Biyao"],["dc.contributor.author","Becker, Andreas"],["dc.contributor.author","Rothenberger, Aribert"],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Herrmann-Lingen, Christoph"],["dc.contributor.author","Meyer, Thomas"],["dc.date.accessioned","2020-12-10T18:15:20Z"],["dc.date.available","2020-12-10T18:15:20Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1080/15622975.2017.1417636"],["dc.identifier.eissn","1814-1412"],["dc.identifier.issn","1562-2975"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/74811"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Attention-deficit/hyperactivity disorder is associated with reduced levels of serum low-density lipoprotein cholesterol in adolescents. Data from the population-based German KiGGS study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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","e1002601"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","PLOS Biology"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","de Oliveira, Rita Machado"],["dc.contributor.author","Vicente Miranda, Hugo"],["dc.contributor.author","Francelle, Laetitia"],["dc.contributor.author","Pinho, Raquel"],["dc.contributor.author","Szegö, Éva M."],["dc.contributor.author","Martinho, Renato"],["dc.contributor.author","Munari, Francesca"],["dc.contributor.author","Lázaro, Diana F."],["dc.contributor.author","Moniot, Sébastien"],["dc.contributor.author","Guerreiro, Patrícia"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2022-03-01T11:44:08Z"],["dc.date.available","2022-03-01T11:44:08Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1371/journal.pbio.1002601"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/102935"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1545-7885"],["dc.relation.iserratumof","/handle/2/43121"],["dc.rights.uri","http://creativecommons.org/licenses/by/4.0/"],["dc.title","Correction: The mechanism of sirtuin 2-mediated exacerbation of alpha-synuclein toxicity in models of Parkinson disease"],["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"]]