Thüne, Katrin

[["dc.bibliographiccitation.firstpage","726"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Antioxidants"],["dc.bibliographiccitation.volume","11"],["dc.contributor.affiliation","Karagianni, Korina; 1Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; korinagk@bio.auth.gr (K.K.); spyrospg@bio.auth.gr (S.P.); lioulia@bio.auth.gr (E.L.)"],["dc.contributor.affiliation","Pettas, Spyros; 1Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; korinagk@bio.auth.gr (K.K.); spyrospg@bio.auth.gr (S.P.); lioulia@bio.auth.gr (E.L.)"],["dc.contributor.affiliation","Kanata, Eirini; 2Neurodegenerative Diseases Research Group, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; ekanata@bio.auth.gr (E.K.); xantho@pharm.auth.gr (K.X.); sklaviad@pharm.auth.gr (T.S.)"],["dc.contributor.affiliation","Lioulia, Elisavet; 1Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; korinagk@bio.auth.gr (K.K.); spyrospg@bio.auth.gr (S.P.); lioulia@bio.auth.gr (E.L.)"],["dc.contributor.affiliation","Thune, Katrin; 3Department of Neurology, German Center for Neurodegenerative Diseases (DZNE), University Medicine Goettingen, 37075 Goettingen, Germany; katrin.thuene@med.uni-goettingen.de (K.T.); matthias.schmitz@med.uni-goettingen.de (M.S.)"],["dc.contributor.affiliation","Schmitz, Matthias; 3Department of Neurology, German Center for Neurodegenerative Diseases (DZNE), University Medicine Goettingen, 37075 Goettingen, Germany; katrin.thuene@med.uni-goettingen.de (K.T.); matthias.schmitz@med.uni-goettingen.de (M.S.)"],["dc.contributor.affiliation","Tsamesidis, Ioannis; 4Department of Prosthodontics, School of Dentistry, Faculty of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; itsamesidis@auth.gr"],["dc.contributor.affiliation","Lymperaki, Evgenia; 5Department of Biomedical Sciences, International Hellenic University, 570 01 Thessaloniki, Greece; evlimper@mls.teithe.gr"],["dc.contributor.affiliation","Xanthopoulos, Konstantinos; 2Neurodegenerative Diseases Research Group, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; ekanata@bio.auth.gr (E.K.); xantho@pharm.auth.gr (K.X.); sklaviad@pharm.auth.gr (T.S.)"],["dc.contributor.affiliation","Sklaviadis, Theodoros; 2Neurodegenerative Diseases Research Group, Department of Pharmacy, School of Health Sciences, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; ekanata@bio.auth.gr (E.K.); xantho@pharm.auth.gr (K.X.); sklaviad@pharm.auth.gr (T.S.)"],["dc.contributor.affiliation","Dafou, Dimitra; 1Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 541 24 Thessaloniki, Greece; korinagk@bio.auth.gr (K.K.); spyrospg@bio.auth.gr (S.P.); lioulia@bio.auth.gr (E.L.)"],["dc.contributor.author","Karagianni, Korina"],["dc.contributor.author","Pettas, Spyros"],["dc.contributor.author","Kanata, Eirini"],["dc.contributor.author","Lioulia, Elisavet"],["dc.contributor.author","Thune, Katrin"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Tsamesidis, Ioannis"],["dc.contributor.author","Lymperaki, Evgenia"],["dc.contributor.author","Xanthopoulos, Konstantinos"],["dc.contributor.author","Sklaviadis, Theodoros"],["dc.contributor.author","Dafou, Dimitra"],["dc.date.accessioned","2022-05-02T08:09:33Z"],["dc.date.available","2022-05-02T08:09:33Z"],["dc.date.issued","2022"],["dc.date.updated","2022-05-05T13:21:13Z"],["dc.description.abstract","Prion diseases are transmissible encephalopathies associated with the conversion of the physiological form of the prion protein (PrPC) to the disease-associated (PrPSc). Despite intense research, no therapeutic or prophylactic agent is available. The catechol-type diterpene Carnosic acid (CA) and its metabolite Carnosol (CS) from Rosmarinus officinalis have well-documented anti-oxidative and neuroprotective effects. Since oxidative stress plays an important role in the pathogenesis of prion diseases, we investigated the potential beneficial role of CA and CS in a cellular model of prion diseases (N2a22L cells) and in a cell-free prion amplification assay (RT-QuIC). The antioxidant effects of the compounds were confirmed when N2a22L were incubated with CA or CS. Furthermore, CA and CS reduced the accumulation of the disease-associated form of PrP, detected by Western Blotting, in N2a22L cells. This effect was validated in RT-QuIC assays, indicating that it is not associated with the antioxidant effects of CA and CS. Importantly, cell-free assays revealed that these natural products not only prevent the formation of PrP aggregates but can also disrupt already formed aggregates. Our results indicate that CA and CS have pleiotropic effects against prion diseases and could evolve into useful prophylactic and/or therapeutic agents against prion and other neurodegenerative diseases."],["dc.description.abstract","Prion diseases are transmissible encephalopathies associated with the conversion of the physiological form of the prion protein (PrPC) to the disease-associated (PrPSc). Despite intense research, no therapeutic or prophylactic agent is available. The catechol-type diterpene Carnosic acid (CA) and its metabolite Carnosol (CS) from Rosmarinus officinalis have well-documented anti-oxidative and neuroprotective effects. Since oxidative stress plays an important role in the pathogenesis of prion diseases, we investigated the potential beneficial role of CA and CS in a cellular model of prion diseases (N2a22L cells) and in a cell-free prion amplification assay (RT-QuIC). The antioxidant effects of the compounds were confirmed when N2a22L were incubated with CA or CS. Furthermore, CA and CS reduced the accumulation of the disease-associated form of PrP, detected by Western Blotting, in N2a22L cells. This effect was validated in RT-QuIC assays, indicating that it is not associated with the antioxidant effects of CA and CS. Importantly, cell-free assays revealed that these natural products not only prevent the formation of PrP aggregates but can also disrupt already formed aggregates. Our results indicate that CA and CS have pleiotropic effects against prion diseases and could evolve into useful prophylactic and/or therapeutic agents against prion and other neurodegenerative diseases."],["dc.identifier.doi","10.3390/antiox11040726"],["dc.identifier.pii","antiox11040726"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107408"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-561"],["dc.relation.eissn","2076-3921"],["dc.title","Carnosic Acid and Carnosol Display Antioxidant and Anti-Prion Properties in In Vitro and Cell-Free Models of Prion Diseases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","95"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Prion"],["dc.bibliographiccitation.lastpage","108"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Arora, Amandeep Singh"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Latif, Umair"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Mihm, Sabine"],["dc.contributor.author","Kumar, Prateek"],["dc.contributor.author","Tahir, Waqas"],["dc.contributor.author","Thüne, Katrin"],["dc.contributor.author","Shafiq, Mohsin"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2020-12-10T18:15:28Z"],["dc.date.available","2020-12-10T18:15:28Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1080/19336896.2020.1729074"],["dc.identifier.eissn","1933-690X"],["dc.identifier.issn","1933-6896"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17401"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/74854"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","The role of cellular prion protein in lipid metabolism in the liver"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","35"],["dc.bibliographiccitation.journal","Acta Neuropathologica Communication"],["dc.bibliographiccitation.lastpage","20"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Fischer, Andre"],["dc.contributor.author","Thüne, Katrin"],["dc.contributor.author","Sikorska, Beata"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Tahir, Waqas"],["dc.contributor.author","Fernández-Borges, Natalia"],["dc.contributor.author","Cramm, Maria"],["dc.contributor.author","Gotzmann, Nadine"],["dc.contributor.author","Carmona, Margarita"],["dc.contributor.author","Streichenberger, Nathalie"],["dc.contributor.author","Michel, Uwe"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Schuetz, Anna-Lena"],["dc.contributor.author","Rajput, Ashish"],["dc.contributor.author","Andréoletti, Olivier"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Liberski, Pawel P."],["dc.contributor.author","Torres, Juan Maria"],["dc.contributor.author","Ferrer, Isidre"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-01-09T14:57:08Z"],["dc.date.available","2018-01-09T14:57:08Z"],["dc.date.issued","2017-04-27"],["dc.description.abstract","Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent form of human prion disease and it is characterized by the presence of neuronal loss, spongiform degeneration, chronic inflammation and the accumulation of misfolded and pathogenic prion protein (PrPSc). The molecular mechanisms underlying these alterations are largely unknown, but the presence of intracellular neuronal calcium (Ca2+) overload, a general feature in models of prion diseases, is suggested to play a key role in prion pathogenesis.Here we describe the presence of massive regulation of Ca2+ responsive genes in sCJD brain tissue, accompanied by two Ca2+-dependent processes: endoplasmic reticulum stress and the activation of the cysteine proteases Calpains 1/2. Pathogenic Calpain proteins activation in sCJD is linked to the cleavage of their cellular substrates, impaired autophagy and lysosomal damage, which is partially reversed by Calpain inhibition in a cellular prion model. Additionally, Calpain 1 treatment enhances seeding activity of PrPSc in a prion conversion assay. Neuronal lysosomal impairment caused by Calpain over activation leads to the release of the lysosomal protease Cathepsin S that in sCJD mainly localises in axons, although massive Cathepsin S overexpression is detected in microglial cells. Alterations in Ca2+ homeostasis and activation of Calpain-Cathepsin axis already occur at pre-clinical stages of the disease as detected in a humanized sCJD mouse model.Altogether our work indicates that unbalanced Calpain-Cathepsin activation is a relevant contributor to the pathogenesis of sCJD at multiple molecular levels and a potential target for therapeutic intervention."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1186/s40478-017-0431-y"],["dc.identifier.pmid","28449707"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14726"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11612"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","2051-5960"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Altered Ca2+ homeostasis induces Calpain-Cathepsin axis activation in sporadic Creutzfeldt-Jakob disease"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","83"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurodegeneration"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Thüne, Katrin"],["dc.contributor.author","Tahir, Waqas"],["dc.contributor.author","Kanata, Eirini"],["dc.contributor.author","Diaz-Lucena, Daniela"],["dc.contributor.author","Xanthopoulos, Konstantinos"],["dc.contributor.author","Kovatsi, Eleni"],["dc.contributor.author","Pleschka, Catharina"],["dc.contributor.author","Garcia-Esparcia, Paula"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Ozbay, Duru"],["dc.contributor.author","Correia, Susana"],["dc.contributor.author","Correia, Ângela"],["dc.contributor.author","Milosevic, Ira"],["dc.contributor.author","Andréoletti, Olivier"],["dc.contributor.author","Fernández-Borges, Natalia"],["dc.contributor.author","Vorberg, Ina M."],["dc.contributor.author","Glatzel, Markus"],["dc.contributor.author","Sklaviadis, Theodoros"],["dc.contributor.author","Torres, Juan Maria"],["dc.contributor.author","Krasemann, Susanne"],["dc.contributor.author","Sánchez-Valle, Raquel"],["dc.contributor.author","Ferrer, Isidro"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2019-07-09T11:44:59Z"],["dc.date.available","2019-07-09T11:44:59Z"],["dc.date.issued","2017"],["dc.description.abstract","Background YKL-40 (also known as Chitinase 3-like 1) is a glycoprotein produced by inflammatory, cancer and stem cells. Its physiological role is not completely understood but YKL-40 is elevated in the brain and cerebrospinal fluid (CSF) in several neurological and neurodegenerative diseases associated with inflammatory processes. Yet the precise characterization of YKL-40 in dementia cases is missing. Methods In the present study, we comparatively analysed YKL-40 levels in the brain and CSF samples from neurodegenerative dementias of different aetiologies characterized by the presence of cortical pathology and disease-specific neuroinflammatory signatures. Results YKL-40 was normally expressed in fibrillar astrocytes in the white matter. Additionally YKL-40 was highly and widely expressed in reactive protoplasmic cortical and perivascular astrocytes, and fibrillar astrocytes in sporadic Creutzfeldt-Jakob disease (sCJD). Elevated YKL-40 levels were also detected in Alzheimer’s disease (AD) but not in dementia with Lewy bodies (DLB). In AD, YKL-40-positive astrocytes were commonly found in clusters, often around β-amyloid plaques, and surrounding vessels with β-amyloid angiopathy; they were also distributed randomly in the cerebral cortex and white matter. YKL-40 overexpression appeared as a pre-clinical event as demonstrated in experimental models of prion diseases and AD pathology. CSF YKL-40 levels were measured in a cohort of 288 individuals, including neurological controls (NC) and patients diagnosed with different types of dementia. Compared to NC, increased YKL-40 levels were detected in sCJD (p < 0.001, AUC = 0.92) and AD (p < 0.001, AUC = 0.77) but not in vascular dementia (VaD) (p > 0.05, AUC = 0.71) or in DLB/Parkinson’s disease dementia (PDD) (p > 0.05, AUC = 0.70). Further, two independent patient cohorts were used to validate the increased CSF YKL-40 levels in sCJD. Additionally, increased YKL-40 levels were found in genetic prion diseases associated with the PRNP-D178N (Fatal Familial Insomnia) and PRNP-E200K mutations. Conclusions Our results unequivocally demonstrate that in neurodegenerative dementias, YKL-40 is a disease-specific marker of neuroinflammation showing its highest levels in prion diseases. Therefore, YKL-40 quantification might have a potential for application in the evaluation of therapeutic intervention in dementias with a neuroinflammatory component."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1186/s13024-017-0226-4"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14995"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59135"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/15151 but duplicate"],["dc.rights","CC BY 4.0"],["dc.rights.access","openAccess"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","220"],["dc.bibliographiccitation.journal","Frontiers in Aging Neuroscience"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Kanata, Eirini"],["dc.contributor.author","Thüne, Katrin"],["dc.contributor.author","Xanthopoulos, Konstantinos"],["dc.contributor.author","Ferrer, Isidre"],["dc.contributor.author","Dafou, Dimitra"],["dc.contributor.author","Zerr, Inga"],["dc.contributor.author","Sklaviadis, Theodoros"],["dc.contributor.author","Llorens, Franc"],["dc.date.accessioned","2019-07-09T11:45:43Z"],["dc.date.available","2019-07-09T11:45:43Z"],["dc.date.issued","2018"],["dc.description.abstract","Prion diseases are transmissible progressive neurodegenerative conditions characterized by rapid neuronal loss accompanied by a heterogeneous neuropathology, including spongiform degeneration, gliosis and protein aggregation. The pathogenic mechanisms and the origins of prion diseases remain unclear on the molecular level. Even though neurodegenerative diseases, including prion diseases, represent distinct entities, their pathogenesis shares a number of features including disturbed protein homeostasis, an overload of protein clearance pathways, the aggregation of pathological altered proteins, and the dysfunction and/or loss of specific neuronal populations. Recently, direct links have been established between neurodegenerative diseases and miRNA dysregulated patterns. miRNAs are a class of small non-coding RNAs involved in the fundamental post-transcriptional regulation of gene expression. Studies of miRNA alterations in the brain and body fluids in human prion diseases provide important insights into potential miRNA-associated disease mechanisms and biomarker candidates. miRNA alterations in prion disease models represent a unique tool to investigate the cause-consequence relationships of miRNA dysregulation in prion disease pathology, and to evaluate the use of miRNAs in diagnosis as biomarkers. Here, we provide an overview of studies on miRNA alterations in human prion diseases and relevant disease models, in relation to pertinent studies on other neurodegenerative diseases."],["dc.identifier.doi","10.3389/fnagi.2018.00220"],["dc.identifier.pmid","30083102"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15293"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59293"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1663-4365"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","610"],["dc.title","MicroRNA Alterations in the Brain and Body Fluids of Humans and Animal Prion Disease Models: Current Status and Perspectives"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Translational Neurodegeneration"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Candelise, Niccolo"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Thüne, Katrin"],["dc.contributor.author","Cramm, Maria"],["dc.contributor.author","Rabano, Alberto"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Stoops, Erik"],["dc.contributor.author","Vanderstichele, Hugo"],["dc.contributor.author","Villar-Pique, Anna"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2020-12-10T18:41:21Z"],["dc.date.available","2020-12-10T18:41:21Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1186/s40035-019-0181-9"],["dc.identifier.eissn","2047-9158"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17126"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77561"],["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","Effect of the micro-environment on α-synuclein conversion and implication in seeded conversion assays"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1006802"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","PLOS Pathogens"],["dc.bibliographiccitation.lastpage","33"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Thüne, Katrin"],["dc.contributor.author","Martí, Eulàlia"],["dc.contributor.author","Kanata, Eirini"],["dc.contributor.author","Dafou, Dimitra"],["dc.contributor.author","Díaz-Lucena, Daniela"],["dc.contributor.author","Vivancos, Ana"],["dc.contributor.author","Shomroni, Orr"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Michel, Uwe"],["dc.contributor.author","Fernández-Borges, Natalia"],["dc.contributor.author","Andréoletti, Olivier"],["dc.contributor.author","del Río, José Antonio"],["dc.contributor.author","Díez, Juana"],["dc.contributor.author","Fischer, Andre"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Sklaviadis, Theodoros"],["dc.contributor.author","Torres, Juan Maria"],["dc.contributor.author","Ferrer, Isidre"],["dc.contributor.author","Zerr, Inga"],["dc.creator.editor","Bartz, Jason C."],["dc.date.accessioned","2018-04-23T11:47:15Z"],["dc.date.available","2018-04-23T11:47:15Z"],["dc.date.issued","2018"],["dc.description.abstract","Increasing evidence indicates that microRNAs (miRNAs) are contributing factors to neurodegeneration. Alterations in miRNA signatures have been reported in several neurodegenerative dementias, but data in prion diseases are restricted to ex vivo and animal models. The present study identified significant miRNA expression pattern alterations in the frontal cortex and cerebellum of sporadic Creutzfeldt-Jakob disease (sCJD) patients. These changes display a highly regional and disease subtype-dependent regulation that correlates with brain pathology. We demonstrate that selected miRNAs are enriched in sCJD isolated Argonaute(Ago)-binding complexes in disease, indicating their incorporation into RNA-induced silencing complexes, and further suggesting their contribution to disease-associated gene expression changes. Alterations in the miRNA-mRNA regulatory machinery and perturbed levels of miRNA biogenesis key components in sCJD brain samples reported here further implicate miRNAs in sCJD gene expression (de)regulation. We also show that a subset of sCJD-altered miRNAs are commonly changed in Alzheimer’s disease, dementia with Lewy bodies and fatal familial insomnia, suggesting potential common mechanisms underlying these neurodegenerative processes. Additionally, we report no correlation between brain and cerebrospinal fluid (CSF) miRNA-profiles in sCJD, indicating that CSF-miRNA profiles do not faithfully mirror miRNA alterations detected in brain tissue of human prion diseases. Finally, utilizing a sCJD MM1 mouse model, we analyzed the miRNA deregulation patterns observed in sCJD in a temporal manner. While fourteen sCJD-related miRNAs were validated at clinical stages, only two of those were changed at early symptomatic phase, suggesting that the miRNAs altered in sCJD may contribute to later pathogenic processes. Altogether, the present work identifies alterations in the miRNA network, biogenesis and miRNA-mRNA silencing machinery in sCJD, whereby contributions to disease mechanisms deserve further investigation."],["dc.identifier.doi","10.1371/journal.ppat.1006802"],["dc.identifier.gro","3142194"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15708"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13314"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.issn","1553-7374"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Regional and subtype-dependent miRNA signatures in sporadic Creutzfeldt-Jakob disease are accompanied by alterations in miRNA silencing machinery and biogenesis"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","198"],["dc.bibliographiccitation.journal","Frontiers in Aging Neuroscience"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Lopez-Gonzalez, Irene"],["dc.contributor.author","Thuene, Katrin"],["dc.contributor.author","Carmona, Margarita"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Andreoletti, Olivier"],["dc.contributor.author","Zerr, Inga"],["dc.contributor.author","Ferrer, Isidre"],["dc.date.accessioned","2018-11-07T09:36:47Z"],["dc.date.available","2018-11-07T09:36:47Z"],["dc.date.issued","2014"],["dc.description.abstract","The present study identifies deregulated cytokines and mediators of the immune response in the frontal cortex and cerebellum of sporadic Creutzfeldt Jakob disease (sCJD) MM1 and VV2 subtypes compared to age-matched controls. Deregulated genes include pro- and anti-inflammatory cytokines, toll-like receptors, colony stimulating factors, cathepsins, members of the complement system, and members of the integrin and CTL/CTLD family with particular regional and sCJD subtype patterns. Analysis of cytokines and mediators at protein level shows expression of selected molecules and receptors in neurons, in astrocytes, and/or in microglia, thus suggesting interactions between neurons and glial cells, mainly microglia, in the neuroinflammatory response in sCJD. Similar inflammatory responses have been shown in the tg340 sCJD MM1 mice, revealing a progressive deregulation of inflammatory mediators with disease progression. Yet, inflammatory molecules involved are subjected to species differences in humans and mice. Moreover, inflammatory-related cell signaling pathways NF kappa B/IKK and JAK/STAT are activated in sCJD and sCJD MM1 mice. Together, the present observations show a self-sustained complex inflammatory and inflammatory-related responses occurring already at early clinical stages in animal model and dramatically progressing at advanced stages of sCJD. Considering this scenario, measures tailored to modulate (activate or inhibit) specific molecules could be therapeutic options in CJD."],["dc.identifier.doi","10.3389/fnagi.2014.00198"],["dc.identifier.isi","000340930200001"],["dc.identifier.pmid","25136317"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11784"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32692"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Frontiers Research Foundation"],["dc.relation.issn","1663-4365"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Subtype and regional-specific neuroinflammation in sporadic Creutzfeldt-Jakob 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"]]