Wagner, Jens

[["dc.bibliographiccitation.firstpage","924"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Journal of Neuropathology and Experimental Neurology"],["dc.bibliographiccitation.lastpage","933"],["dc.bibliographiccitation.volume","74"],["dc.contributor.author","Shi, Song"],["dc.contributor.author","Wagner, Jens"],["dc.contributor.author","Mitteregger-Kretzschmar, Gerda"],["dc.contributor.author","Ryazanov, Sergey"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Giese, Armin"],["dc.date.accessioned","2017-09-07T11:43:35Z"],["dc.date.available","2017-09-07T11:43:35Z"],["dc.date.issued","2015"],["dc.description.abstract","Prion diseases are fatal neurodegenerative diseases characterized by accumulation of the pathogenic prion protein PrPSc in the brain. We established quantitative real-time quaking-induced conversion for the measurement of minute amounts of PrPSc in body fluids such as urine. Using this approach, we monitored the efficacy of antiprion therapy by quantifying the seeding activity of PrPSc from the brain and urine of mice after prion infection. We found that the aggregation inhibitor anle138b decreased the levels of PrPSc in the brain and urine. Importantly, variations of PrPSc levels in the urine closely corresponded to those in the brain. Our findings indicate that quantification of urinary PrPSc enables measurement of prion disease progression in body fluids and can substitute for immunodetection in brain tissue. We expect PrPSc quantification biologic fluids (such as urine and cerebrospinal fluid) with quantitative real-time quaking-induced conversion to emerge as a valuable noninvasive diagnostic tool for monitoring disease progression and the efficacy of therapeutic approaches in animal studies and human clinical trials of prion diseases. Moreover, highly sensitive methods for quantifying pathologic aggregate seeds might provide novel molecular biomarkers for other neurodegenerative diseases that may involve prion-like mechanisms (protein aggregation and spreading), such as Alzheimer disease and Parkinson disease."],["dc.identifier.doi","10.1097/NEN.0000000000000233"],["dc.identifier.gro","3141840"],["dc.identifier.isi","000360142900007"],["dc.identifier.pmid","26247395"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1656"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0022-3069"],["dc.title","Quantitative Real-Time Quaking-Induced Conversion Allows Monitoring of Disease-Modifying Therapy in the Urine of Prion-Infected Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","619"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Acta Neuropathologica"],["dc.bibliographiccitation.lastpage","631"],["dc.bibliographiccitation.volume","130"],["dc.contributor.author","Wagner, J."],["dc.contributor.author","Krauss, S."],["dc.contributor.author","Shi, S."],["dc.contributor.author","Ryazanov, S."],["dc.contributor.author","Steffen, J."],["dc.contributor.author","Miklitz, C."],["dc.contributor.author","Leonov, A."],["dc.contributor.author","Kleinknecht, A."],["dc.contributor.author","Goericke, Bettina"],["dc.contributor.author","Weishaupt, J. H."],["dc.contributor.author","Weckbecker, D."],["dc.contributor.author","Reiner, A. M."],["dc.contributor.author","Zinth, W."],["dc.contributor.author","Levin, J."],["dc.contributor.author","Ehninger, D."],["dc.contributor.author","Remy, S."],["dc.contributor.author","Kretzschmar, Hans A."],["dc.contributor.author","Griesinger, C."],["dc.contributor.author","Giese, A."],["dc.contributor.author","Fuhrmann, M."],["dc.date.accessioned","2017-09-07T11:43:27Z"],["dc.date.available","2017-09-07T11:43:27Z"],["dc.date.issued","2015"],["dc.description.abstract","Pathological tau aggregation leads to filamentous tau inclusions and characterizes neurodegenerative tauopathies such as Alzheimer's disease and frontotemporal dementia and parkinsonism linked to chromosome 17. Tau aggregation coincides with clinical symptoms and is thought to mediate neurodegeneration. Transgenic mice overexpressing mutant human P301S tau exhibit many neuropathological features of human tauopathies including behavioral deficits and increased mortality. Here, we show that the di-phenyl-pyrazole anle138b binds to aggregated tau and inhibits tau aggregation in vitro and in vivo. Furthermore, anle138b treatment effectively ameliorates disease symptoms, increases survival time and improves cognition of tau transgenic PS19 mice. In addition, we found decreased synapse and neuron loss accompanied by a decreased gliosis in the hippocampus. Our results suggest that reducing tau aggregates with anle138b may represent an effective and promising approach for the treatment of human tauopathies."],["dc.identifier.doi","10.1007/s00401-015-1483-3"],["dc.identifier.gro","3141799"],["dc.identifier.isi","000363270100002"],["dc.identifier.pmid","26439832"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1201"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1432-0533"],["dc.relation.issn","0001-6322"],["dc.title","Reducing tau aggregates with anle138b delays disease progression in a mouse model of tauopathies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]