Correia, Susana

[["dc.bibliographiccitation.firstpage","697"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Molecular Neurobiology"],["dc.bibliographiccitation.lastpage","709"],["dc.bibliographiccitation.volume","54"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Younas, Neelam"],["dc.contributor.author","Correia, Susana"],["dc.contributor.author","Shafiq, Mohsin"],["dc.contributor.author","Tahir, Waqas"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Ferrer, Isidre"],["dc.contributor.author","Andreoletti, Olivier"],["dc.contributor.author","Zerr, Inga"],["dc.date.accessioned","2018-11-07T10:29:22Z"],["dc.date.available","2018-11-07T10:29:22Z"],["dc.date.issued","2017"],["dc.description.abstract","There is an increasing demand for the understanding of pathophysiology on neurodegeneration diseases at early stages. Changes in endocytic machinery and the cytoskeleton-associated response are the first alterations observed in Creutzfeldt-Jakob disease (CJD) and Alzheimer's disease AD brain. In this study, we performed a targeted search for endocytic pathway proteins in the different regions of the brain. We found late endosome marker Rab7a which was significantly upregulated in the frontal cortex region in the rapid progressive CJD form (MM1) and rapid progressive AD (rpAD) forms. However, Rab9 expression was significantly downregulated only in CJD-MM1 brain frontal cortex region. In the cerebellum, Rab7a expression showed significant upregulation in both subtype MM1 and VV2 CJD forms, in contrast to Rab9 which showed significant downregulation in both subtype MM1 and VV2 CJD forms at terminal stage of the disease. To check regulatory response at pre-symptomatic stage of the disease, we checked the regulatory interactive response of Rab7a, Rab9, and known biomarkers PrPC and tau forms in frontal cortex at pre-symptomatic stage of the disease in tg340 mice expressing about fourfold of human PrP-M129 with PrP-null background that had been inoculated with human sCJD MM1 brain tissue homogenates (sCJD MM1 mice). In addition, we analyzed 5XFAD mice, exhibiting five mutations in the APP and presenilin genes related to familial Alzheimer's disease (FAD), to validate specific regulatory response of Rab7a, Rab9, tau, and phosphorylated form of tau by immunostaining 5XFAD mice in comparison with the wild-type age-matched mice brain. The cortical region of 5XFAD mice brain showed accumulated form of Rab7a in puncta that co-label for p-Tau, indicating colocalization by using confocal laser-scanning microscopy and was confirmed by using reverse co-immunoprecipitation. Furthermore, synthetic RNA (siRNA) against the Rab7a gene decreased expression of Rab7a protein, in cortical primary neuronal cultures of PrPC wild type. This depleted expression of Rab7a led to the increased accumulation of PrPC in Rab9-positive endosomal compartments and consequently an increased co-localization between PrPC/Rab9; however, total tau level decreased. Interestingly, siRNA against tau gene in cortical primary neuronal cultures of PrPC wild-type mice showed enhanced Rab7a and Rab9 expression and increase formation of dendritic spines. The work described highlighted the selective involvement of late endosomal compartment marker Rab7a in CJD, slow and rapid progressive forms of AD pathogenesis."],["dc.identifier.doi","10.1007/s12035-016-9694-8"],["dc.identifier.isi","000392133900058"],["dc.identifier.pmid","26768426"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/43631"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Humana Press Inc"],["dc.relation.issn","1559-1182"],["dc.relation.issn","0893-7648"],["dc.title","Strain-Specific Altered Regulatory Response of Rab7a and Tau in Creutzfeldt-Jakob Disease and Alzheimer's Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["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","mds.28774"],["dc.bibliographiccitation.firstpage","39"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Movement Disorders"],["dc.bibliographiccitation.lastpage","51"],["dc.bibliographiccitation.volume","37"],["dc.contributor.affiliation","Thom, Tobias; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Fischer, Anna‐Lisa; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Correia, Angela; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Correia, Susana; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Llorens, Franc; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Pique, Anna‐Villar; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Möbius, Wiebke; 4\r\nDepartment for Neurogenetics\r\nEM Core Unit Max Planck Institute for Experimental Medicine\r\nGöttingen Germany"],["dc.contributor.affiliation","Domingues, Renato; 5\r\nDepartment of Experimental Neurodegeneration\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Zafar, Saima; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Stoops, Erik; 7\r\nADx NeuroSciences\r\nGhent Belgium"],["dc.contributor.affiliation","Silva, Christopher J.; 8\r\nProduce Safety & Microbiology Research Unit, Western Regional Research Center, United States Department of Agriculture\r\nAgricultural Research Service\r\nAlbany California USA"],["dc.contributor.affiliation","Fischer, Andre; 9\r\nDepartment for Epigenetics and Systems Medicine in Neurodegenerative Diseases\r\nGerman Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.affiliation","Outeiro, Tiago F.; 5\r\nDepartment of Experimental Neurodegeneration\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Zerr, Inga; 1\r\nDepartment of Neurology\r\nUniversity Medical Center Göttingen and the German Center for Neurodegenerative Diseases\r\nGöttingen Germany"],["dc.contributor.author","Thom, Tobias"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Fischer, Anna‐Lisa"],["dc.contributor.author","Correia, Angela"],["dc.contributor.author","Correia, Susana"],["dc.contributor.author","Llorens, Franc"],["dc.contributor.author","Pique, Anna‐Villar"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Domingues, Renato"],["dc.contributor.author","Zafar, Saima"],["dc.contributor.author","Zerr, Inga"],["dc.contributor.author","Stoops, Erik"],["dc.contributor.author","Silva, Christopher J."],["dc.contributor.author","Fischer, André"],["dc.contributor.author","Outeiro, Tiago F."],["dc.date.accessioned","2021-09-01T06:42:58Z"],["dc.date.available","2021-09-01T06:42:58Z"],["dc.date.issued","2021"],["dc.date.updated","2022-03-21T12:51:34Z"],["dc.description.abstract","Abstract Background The cellular prion protein (PrPC) is a membrane‐bound, multifunctional protein mainly expressed in neuronal tissues. Recent studies indicate that the native trafficking of PrPC can be misused to internalize misfolded amyloid beta and α‐synuclein (aSyn) oligomers. Objectives We define PrPC's role in internalizing misfolded aSyn in α‐synucleinopathies and identify further involved proteins. Methods We performed comprehensive behavioral studies on four transgenic mouse models (ThySyn and ThySynPrP00, TgM83 and TgMPrP00) at different ages. We developed PrPC‐(over)‐expressing cell models (cell line and primary cortical neurons), used confocal laser microscopy to perform colocalization studies, applied mass spectrometry to identify interactomes, and determined disassociation constants using surface plasmon resonance (SPR) spectroscopy. Results Behavioral deficits (memory, anxiety, locomotion, etc.), reduced lifespans, and higher oligomeric aSyn levels were observed in PrPC‐expressing mice (ThySyn and TgM83), but not in homologous Prnp ablated mice (ThySynPrP00 and TgMPrP00). PrPC colocalized with and facilitated aSyn (oligomeric and monomeric) internalization in our cell‐based models. Glimepiride treatment of PrPC‐overexpressing cells reduced aSyn internalization in a dose‐dependent manner. SPR analysis showed that the binding affinity of PrPC to monomeric aSyn was lower than to oligomeric aSyn. Mass spectrometry‐based proteomic studies identified clathrin in the immunoprecipitates of PrPC and aSyn. SPR was used to show that clathrin binds to recombinant PrP, but not aSyn. Experimental disruption of clathrin‐coated vesicles significantly decreased aSyn internalization. Conclusion PrPC's native trafficking can be misused to internalize misfolded aSyn through a clathrin‐based mechanism, which may facilitate the spreading of pathological aSyn. Disruption of aSyn‐PrPC binding is, therefore, an appealing therapeutic target in α‐synucleinopathies. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society"],["dc.description.sponsorship","ADDF http://dx.doi.org/10.13039/100002565"],["dc.description.sponsorship","Fondo de Investigación Sanitaria"],["dc.identifier.doi","10.1002/mds.28774"],["dc.identifier.pmid","34448510"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89190"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/335"],["dc.identifier.url","https://sfb1286.uni-goettingen.de/literature/publications/130"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1286: Quantitative Synaptologie"],["dc.relation.eissn","1531-8257"],["dc.relation.issn","0885-3185"],["dc.relation.workinggroup","RG A. Fischer (Epigenetics and Systems Medicine in Neurodegenerative Diseases)"],["dc.relation.workinggroup","RG Möbius"],["dc.relation.workinggroup","RG Outeiro (Experimental Neurodegeneration)"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","Cellular Prion Protein Mediates α‐Synuclein Uptake, Localization, and Toxicity In Vitro and In Vivo"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]