Francelle, Laetitia

[["dc.bibliographiccitation.artnumber","17"],["dc.bibliographiccitation.journal","Frontiers in Human Neuroscience"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Francelle, Laetitia"],["dc.contributor.author","Lotz, Caroline"],["dc.contributor.author","Outeiro, Tiago"],["dc.contributor.author","Brouillet, Emmanuel"],["dc.contributor.author","Merienne, Karine"],["dc.date.accessioned","2018-11-07T10:28:14Z"],["dc.date.available","2018-11-07T10:28:14Z"],["dc.date.issued","2017"],["dc.description.abstract","Unbalanced epigenetic regulation is thought to contribute to the progression of several neurodegenerative diseases, including Huntington's disease (HD), a genetic disorder considered as a paradigm of epigenetic dysregulation. In this review, we attempt to address open questions regarding the role of epigenetic changes in HD, in the light of recent advances in neuroepigenetics. We particularly discuss studies using genome-wide scale approaches that provide insights into the relationship between epigenetic regulations, gene expression and neuronal activity in normal and diseased neurons, including HD neurons. We propose that cell-type specific techniques and 3D based methods will advance knowledge of epigenome in the context of brain region vulnerability in neurodegenerative diseases. A better understanding of the mechanisms underlying epigenetic changes and of their consequences in neurodegenerative diseases is required to design therapeutic strategies more effective than current strategies based on histone deacetylase (HDAC) inhibitors. Researches in HD may play a driving role in this process."],["dc.identifier.doi","10.3389/fnhum.2017.00017"],["dc.identifier.isi","000392986400001"],["dc.identifier.pmid","28194101"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14318"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43381"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Frontiers Media Sa"],["dc.relation.issn","1662-5161"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Contribution of Neuroepigenetics to Huntington's Disease"],["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.firstpage","76"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Human Molecular Genetics"],["dc.bibliographiccitation.lastpage","85"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Blum, David"],["dc.contributor.author","Herrera, Federico"],["dc.contributor.author","Francelle, Laetitia"],["dc.contributor.author","Mendes, Tiago"],["dc.contributor.author","Basquin, Marie"],["dc.contributor.author","Obriot, Helene"],["dc.contributor.author","Demeyer, Dominique"],["dc.contributor.author","Sergeant, Nicolas"],["dc.contributor.author","Gerhardt, Ellen"],["dc.contributor.author","Brouillet, Emmanuel"],["dc.contributor.author","Buée, Luc"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.date.accessioned","2018-11-07T10:03:30Z"],["dc.date.available","2018-11-07T10:03:30Z"],["dc.date.issued","2015"],["dc.description.abstract","Tau abnormalities play a central role in several neurodegenerative diseases, collectively known as tauopathies. In the present study, we examined whether mutant huntingtin (mHtt), which causes Huntington's disease (HD), modifies Tau phosphorylation and subcellular localization using cell and mouse HD models. Initially, we used novel bimolecular fluorescence complementation assays in live cells to evaluate Tau interactions with either wild type (25QHtt) ormutant huntingtin(103QHtt). While 25QHtt and Tau interacted at the level of the microtubule network, 103QHtt and Tau interacted and formed 'ring-like' inclusions localized in the vicinity of the microtubular organizing center (MTOC). Fluorescence recovery after photobleaching experiments also indicated that, whereas homomeric 103QHtt/103QHtt pairs rapidly re-entered into inclusions, heteromeric 103QHtt/Tau pairs remained excluded from the 'ring-like' inclusions. Interestingly, in vitro Tau relocalization was associated to Tau hyperphosphorylation. Consistent with this observation, we found strong Tau hyperphosphorylation in brain samples from two different mouse models of HD, R6/2 and 140CAG knock-in. This was associated with a significant reduction in the levels of Tau phosphatases (PP1, PP2A and PP2B), with no apparent involvement of major Tau kinases. Thus, the present study strongly suggests that expression of mHtt leads to Tau hyperphosphorylation, relocalization and sequestration through direct protein-protein interactions in inclusion-like compartments in the vicinity of the MTOC. Likewise, our data also suggest that Tau alterations may also contribute to HD pathogenesis."],["dc.identifier.doi","10.1093/hmg/ddu421"],["dc.identifier.isi","000350135400007"],["dc.identifier.pmid","25143394"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38481"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1460-2083"],["dc.relation.issn","0964-6906"],["dc.title","Mutant huntingtin alters Tau phosphorylation and subcellular distribution"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Francelle, Laetitia"],["dc.contributor.author","Outeiro, Tiago F."],["dc.contributor.author","Rappold, Gudrun A."],["dc.date.accessioned","2021-04-14T08:26:46Z"],["dc.date.available","2021-04-14T08:26:46Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1038/s41598-020-62678-5"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82069"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","2045-2322"],["dc.title","Inhibition of HDAC6 activity protects dopaminergic neurons from alpha-synuclein toxicity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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","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","435"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Hippocampus"],["dc.bibliographiccitation.lastpage","449"],["dc.bibliographiccitation.volume","27"],["dc.contributor.author","Pardo, Joaquin"],["dc.contributor.author","Abba, Martin C."],["dc.contributor.author","Lacunza, Ezequiel"],["dc.contributor.author","Francelle, Laetitia"],["dc.contributor.author","Morel, Gustavo R."],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Goya, Rodolfo G."],["dc.date.accessioned","2018-11-07T10:25:44Z"],["dc.date.available","2018-11-07T10:25:44Z"],["dc.date.issued","2017"],["dc.description.abstract","There have been a few descriptive studies in aged rodents about transcriptome changes in the hippocampus, most of them in males. Here, we assessed the age changes in spatial memory performance and hippocampal morphology in female rats and compared those changes with changes in the hippocampal transcriptome. Old rats displayed significant deficits in spatial memory. In both age groups, hole exploration frequency showed a clear peak at hole 0 (escape hole), but the amplitude of the peak was significantly higher in the young than in the old animals. In the hippocampus, there was a dramatic reduction in neurogenesis, whereas reactive microglial infiltrates revealed an inflammatory hippocampal state in the senile rats. Hippocampal RNA-sequencing showed that 210 genes are differentially expressed in the senile rats, most of them being downregulated. Our RNA-Seq data showed that various genes involved in the immune response, including TYROBP, CD11b, C3, CD18, CD4, and CD74, are overexpressed in the hippocampus of aged female rats. Enrichment analysis showed that the pathways overrepresented in the senile rats matched those of an exacerbated inflammatory environment, reinforcing our morphologic findings. After correlating our results with public data of human and mouse hippocampal gene expression, we found an 11-gene signature of overexpressed genes related to inflammatory processes that was conserved across species. We conclude that age-related hippocampal deficits in female rats share commonalities between human and rodents. Interestingly, the 11-gene signature that we identified may represent a cluster of immune and regulatory genes that are deregulated in the hippocampus and possibly other brain regions during aging as well as in some neurodegenerative diseases and low-grade brain tumors. Our study further supports neuroinflammation as a promising target to treat cognitive dysfunction in old individuals and some brain tumors. (c) 2017 Wiley Periodicals, Inc."],["dc.identifier.doi","10.1002/hipo.22703"],["dc.identifier.isi","000397504500008"],["dc.identifier.pmid","28085212"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42914"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley"],["dc.relation.issn","1098-1063"],["dc.relation.issn","1050-9631"],["dc.title","Identification of a conserved gene signature associated with an exacerbated inflammatory environment in the hippocampus of aging rats"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]