Zafar, Saima

[["dc.bibliographiccitation.journal","Molecular Neurobiology"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Younas, Neelam"],["dc.contributor.author","Sheikh, Nadeem"],["dc.contributor.author","Tahir, Waqas"],["dc.contributor.author","Shafiq, Mohsin"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Ferrer, Isidre"],["dc.contributor.author","Andréoletti, Olivier"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2020-12-10T14:14:25Z"],["dc.date.available","2020-12-10T14:14:25Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1007/s12035-017-0589-0"],["dc.identifier.eissn","1559-1182"],["dc.identifier.issn","0893-7648"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71344"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Cytoskeleton-Associated Risk Modifiers Involved in Early and Rapid Progression of Sporadic Creutzfeldt-Jakob Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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","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","e1006759"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","PLoS Pathogens"],["dc.bibliographiccitation.lastpage","6"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Shafiq, Mohsin"],["dc.contributor.author","Andréoletti, Olivier"],["dc.contributor.author","Zerr, Inga"],["dc.contributor.editor","True, Heather L."],["dc.date.accessioned","2021-11-22T14:31:43Z"],["dc.date.available","2021-11-22T14:31:43Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1371/journal.ppat.1006759"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15707"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/93398"],["dc.language.iso","en"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/15709 but duplicate"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.issn","1553-7374"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Animal TSEs and public health: What remains of past lessons?"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","517"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurobiology"],["dc.bibliographiccitation.lastpage","537"],["dc.bibliographiccitation.volume","55"],["dc.contributor.author","Tahir, Waqas"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Arora, Amandeep Singh"],["dc.contributor.author","Thüne, Katrin"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Gotzmann, Nadine"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Torres, Juan Maria"],["dc.contributor.author","Andréoletti, Olivier"],["dc.contributor.author","Ferrer, Isidre"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2020-12-10T14:14:25Z"],["dc.date.available","2020-12-10T14:14:25Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1007/s12035-016-0294-4"],["dc.identifier.eissn","1559-1182"],["dc.identifier.issn","0893-7648"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/71342"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Molecular Alterations in the Cerebellum of Sporadic Creutzfeldt–Jakob Disease Subtypes with DJ-1 as a Key Regulator of Oxidative Stress"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]