Götz, Alexander A.

[["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.journal","Glia"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Goetz, Alexander A."],["dc.contributor.author","Nau, R."],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Hanisch, U-K"],["dc.date.accessioned","2018-11-07T09:23:23Z"],["dc.date.available","2018-11-07T09:23:23Z"],["dc.date.issued","2013"],["dc.format.extent","S181"],["dc.identifier.isi","000320408400581"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29563"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.conference","11th European Meeting on Glial Cell Function in Health and Disease"],["dc.relation.eventlocation","Berlin, GERMANY"],["dc.relation.issn","0894-1491"],["dc.title","CD14 AS A KEY REGULATOR OF TLR-MEDIATED RESPONSES OF MICROGLIA"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","635"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","649"],["dc.bibliographiccitation.volume","64"],["dc.contributor.author","Janova, Hana"],["dc.contributor.author","Böttcher, Chotima"],["dc.contributor.author","Holtman, Inge R."],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Rossum, Denise van"],["dc.contributor.author","Götz, Alexander"],["dc.contributor.author","Ernst, Anne-Sophie"],["dc.contributor.author","Fritsche, Christin"],["dc.contributor.author","Gertig, Ulla"],["dc.contributor.author","Saiepour, Nasrin"],["dc.contributor.author","Gronke, Konrad"],["dc.contributor.author","Wrzos, Claudia"],["dc.contributor.author","Ribes, Sandra"],["dc.contributor.author","Rolfes, Simone"],["dc.contributor.author","Weinstein, Jonathan"],["dc.contributor.author","Ehrenreich, Hannelore"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Kopatz, Jens"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Salinas-Riester, Gabriela"],["dc.contributor.author","Weber, Martin S."],["dc.contributor.author","Prinz, Marco"],["dc.contributor.author","Brück, Wolfgang"],["dc.contributor.author","Eggen, Bart J. L."],["dc.contributor.author","Boddeke, Hendrikus W. G. M."],["dc.contributor.author","Priller, Josef"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.date.accessioned","2017-09-07T11:45:34Z"],["dc.date.available","2017-09-07T11:45:34Z"],["dc.date.issued","2016"],["dc.description.abstract","Microglia, innate immune cells of the CNS, sense infection and damage through overlapping receptor sets. Toll-like receptor (TLR) 4 recognizes bacterial lipopolysaccharide (LPS) and multiple injury-associated factors. We show that its co-receptor CD14 serves three non-redundant functions in microglia. First, it confers an up to 100-fold higher LPS sensitivity compared to peripheral macrophages to enable efficient proinflammatory cytokine induction. Second, CD14 prevents excessive responses to massive LPS challenges via an interferon β-mediated feedback. Third, CD14 is mandatory for microglial reactions to tissue damage-associated signals. In mice, these functions are essential for balanced CNS responses to bacterial infection, traumatic and ischemic injuries, since CD14 deficiency causes either hypo- or hyperinflammation, insufficient or exaggerated immune cell recruitment or worsened stroke outcomes. While CD14 orchestrates functions of TLR4 and related immune receptors, it is itself regulated by TLR and non-TLR systems to thereby fine-tune microglial damage-sensing capacity upon infectious and non-infectious CNS challenges."],["dc.identifier.doi","10.1002/glia.22955"],["dc.identifier.gro","3150405"],["dc.identifier.pmid","26683584"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7166"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.issn","0894-1491"],["dc.title","CD14 is a key organizer of microglial responses to CNS infection and injury"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]