Menzfeld, Christiane

[["dc.bibliographiccitation.firstpage","1083"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","1099"],["dc.bibliographiccitation.volume","63"],["dc.contributor.author","Menzfeld, Christiane"],["dc.contributor.author","John, Michael"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Goetz, Alexander A."],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Nau, Roland"],["dc.contributor.author","Borisch, Angela"],["dc.contributor.author","Boutin, Philippe"],["dc.contributor.author","Neumann, Konstantin"],["dc.contributor.author","Bremes, Vanessa"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Tischner, Denise"],["dc.contributor.author","Waetzig, Vicky"],["dc.contributor.author","Herdegen, Thomas"],["dc.contributor.author","Teismann, Peter"],["dc.contributor.author","Greig, Iain"],["dc.contributor.author","Mueller, Michael"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Mildner, Alexander"],["dc.contributor.author","Kettenmann, Helmut"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Prinz, Marco R."],["dc.contributor.author","Rotshenker, Shlomo"],["dc.contributor.author","Weber, Martin S."],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.date.accessioned","2018-11-07T09:56:53Z"],["dc.date.available","2018-11-07T09:56:53Z"],["dc.date.issued","2015"],["dc.description.abstract","The putative protein tyrosine kinase (PTK) inhibitor tyrphostin AG126 has proven beneficial in various models of inflammatory disease. Yet molecular targets and cellular mechanisms remained enigmatic. We demonstrate here that AG126 treatment has beneficial effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. AG126 alleviates the clinical symptoms, diminishes encephalitogenic Th17 differentiation, reduces inflammatory CNS infiltration as well as microglia activation and attenuates myelin damage. We show that AG126 directly inhibits Bruton's tyrosine kinase (BTK), a PTK associated with B cell receptor and Toll-like receptor (TLR) signaling. However, BTK inhibition cannot account for the entire activity spectrum. Effects on TLR-induced proinflammatory cytokine expression in microglia involve AG126 hydrolysis and conversion of its dinitrile side chain to malononitrile (MN). Notably, while liberated MN can subsequently mediate critical AG126 features, full protection in EAE still requires delivery of intact AG126. Its anti-inflammatory potential and especially interference with TLR signaling thus rely on a dual mechanism encompassing BTK and a novel MN-sensitive target. Both principles bear great potential for the therapeutic management of disturbed innate and adaptive immune functions. GLIA 2015;63:1083-1099"],["dc.identifier.doi","10.1002/glia.22803"],["dc.identifier.isi","000353244400011"],["dc.identifier.pmid","25731696"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37056"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1098-1136"],["dc.relation.issn","0894-1491"],["dc.title","Tyrphostin AG126 Exerts Neuroprotection in CNS Inflammation by a Dual Mechanism"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.volume","57"],["dc.contributor.author","Menzfeld, Christiane"],["dc.contributor.author","John, Michael"],["dc.contributor.author","Neumann, K."],["dc.contributor.author","Tischner, Denise"],["dc.contributor.author","Wienands, Juergen"],["dc.contributor.author","Reichardt, Holger Michael"],["dc.contributor.author","Luehder, Fred"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Rotshenker, Shlomo"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.date.accessioned","2018-11-07T11:23:41Z"],["dc.date.available","2018-11-07T11:23:41Z"],["dc.date.issued","2009"],["dc.format.extent","S66"],["dc.identifier.isi","000270075500275"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56240"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-liss"],["dc.publisher.place","Hoboken"],["dc.relation.conference","9th European Meeting on Glial Cells in Health and Disease"],["dc.relation.eventlocation","Paris, FRANCE"],["dc.relation.issn","0894-1491"],["dc.title","TYRPHOSTIN AG126 MODULATES TOLL-LIKE RECEPTOR (TLR)-ACTIVATED RESPONSES IN MICROGLIA"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","102"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neurobiology of Disease"],["dc.bibliographiccitation.lastpage","114"],["dc.bibliographiccitation.volume","48"],["dc.contributor.author","Grosser, Emanuel"],["dc.contributor.author","Hirt, Ursula"],["dc.contributor.author","Janc, Oliwia A."],["dc.contributor.author","Menzfeld, Christiane"],["dc.contributor.author","Fischer, Marc"],["dc.contributor.author","Kempkes, Belinda"],["dc.contributor.author","Vogelgesang, Steffen"],["dc.contributor.author","Manzke, Till U."],["dc.contributor.author","Opitz, Lennart"],["dc.contributor.author","Salinas-Riester, Gabriela"],["dc.contributor.author","Müller, Michael"],["dc.date.accessioned","2018-09-28T10:18:29Z"],["dc.date.available","2018-09-28T10:18:29Z"],["dc.date.issued","2012"],["dc.description.abstract","Rett syndrome is an X chromosome-linked neurodevelopmental disorder associated with cognitive impairment, motor dysfunction and breathing irregularities causing intermittent hypoxia. Evidence for impaired mitochondrial function is also accumulating. A subunit of complex III is among the potentially dys-regulated genes, the inner mitochondrial membrane is leaking protons, brain ATP levels seem reduced, and Rett patient blood samples confirm increased oxidative damage. We therefore screened for mitochondrial dysfunction and impaired redox balance. In hippocampal slices of a Rett mouse model (Mecp2(-/y)) we detected an increased FAD/NADH baseline-ratio indicating intensified oxidization. Cyanide-induced anoxia caused similar decreases in FAD/NADH ratio and mitochondrial membrane potential in both genotypes, but Mecp2(-/y) mitochondria seemed less polarized. Quantifying cytosolic redox balance with the genetically-encoded optical probe roGFP1 confirmed more oxidized baseline conditions, a more vulnerable redox-balance, and more intense responses of Mecp2(-/y) hippocampus to oxidative challenge and mitochondrial impairment. Trolox treatment improved the redox baseline of Mecp2(-/y) hippocampus and dampened its exaggerated responses to oxidative challenge. Microarray analysis of the hippocampal CA1 subfield did not detect alterations of key mitochondrial enzymes or scavenging systems. Yet, quantitative PCR confirmed a moderate upregulation of superoxide dismutase 1 in Mecp2(-/y) hippocampus, which might be a compensatory response to the increased oxidative burden. Since several receptors and ion-channels are redox-modulated, the mitochondrial and redox changes which already manifest in neonates could contribute to the hyperexcitability and diminished synaptic plasticity in MeCP2 deficiency. Therefore, targeting cellular redox balance might qualify as a potential pharmacotherapeutic approach to improve neuronal network function in Rett syndrome."],["dc.identifier.doi","10.1016/j.nbd.2012.06.007"],["dc.identifier.pmid","22750529"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15855"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1095-953X"],["dc.title","Oxidative burden and mitochondrial dysfunction in a mouse model of Rett syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]