Gold, Ralf

[["dc.bibliographiccitation.artnumber","e7624"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","PLoS One"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Linker, Ralf A."],["dc.contributor.author","Brechlin, Peter"],["dc.contributor.author","Jesse, Sarah"],["dc.contributor.author","Steinacker, Petra"],["dc.contributor.author","Lee, D. H."],["dc.contributor.author","Asif, Abdul R."],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Tumani, Hayrettin"],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Otto, Markus"],["dc.date.accessioned","2019-07-09T11:52:40Z"],["dc.date.available","2019-07-09T11:52:40Z"],["dc.date.issued","2009-10-28"],["dc.description.abstract","The identification of new biomarkers is of high interest for the prediction of the disease course and also for the identification of pathomechanisms in multiple sclerosis (MS). To specify markers of the chronic disease phase, we performed proteome profiling during the later phase of myelin oligodendrocyte glycoprotein induced experimental autoimmune encephalomyelitis (MOG-EAE, day 35 after immunization) as a model disease mimicking many aspects of secondary progressive MS. In comparison to healthy controls, high resolution 2 dimensional gel electrophoresis revealed a number of regulated proteins, among them glial fibrilary acidic protein (GFAP). Phase specific up-regulation of GFAP in chronic EAE was confirmed by western blotting and immunohistochemistry. Protein levels of GFAP were also increased in the cerebrospinal fluid of MS patients with specificity for the secondary progressive disease phase. In a next step, proteome profiling of an EAE model with enhanced degenerative mechanisms revealed regulation of alpha-internexin, syntaxin binding protein 1, annexin V and glutamate decarboxylase in the ciliary neurotrophic factor (CNTF) knockout mouse. The identification of these proteins implicate an increased apoptosis and enhanced axonal disintegration and correlate well the described pattern of tissue injury in CNTF -/- mice which involve oligodendrocyte (OL) apoptosis and axonal injury.In summary, our findings underscore the value of proteome analyses as screening method for stage specific biomarkers and for the identification of new culprits for tissue damage in chronic autoimmune demyelination."],["dc.format.extent","9"],["dc.identifier.doi","10.1371/journal.pone.0007624"],["dc.identifier.fs","544326"],["dc.identifier.pmid","19865482"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5819"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60250"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.subject.ddc","610"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Apoptosis"],["dc.subject.mesh","Axons"],["dc.subject.mesh","Disease Models, Animal"],["dc.subject.mesh","Encephalomyelitis, Autoimmune, Experimental"],["dc.subject.mesh","Gene Expression Profiling"],["dc.subject.mesh","Gene Expression Regulation"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Mice, Inbred C57BL"],["dc.subject.mesh","Mice, Transgenic"],["dc.subject.mesh","Multiple Sclerosis"],["dc.subject.mesh","Oligodendroglia"],["dc.subject.mesh","Proteome"],["dc.subject.mesh","Proteomics"],["dc.subject.mesh","Time Factors"],["dc.title","Proteome profiling in murine models of multiple sclerosis: identification of stage specific markers and culprits for tissue damage."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","8434"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Journal of immunology (Baltimore, Md. : 1950)"],["dc.bibliographiccitation.lastpage","8443"],["dc.bibliographiccitation.volume","180"],["dc.contributor.author","Wüst, Simone"],["dc.contributor.author","van den Brandt, Jens"],["dc.contributor.author","Tischner, Denise"],["dc.contributor.author","Kleiman, Anna"],["dc.contributor.author","Tuckermann, Jan P."],["dc.contributor.author","Gold, Ralf"],["dc.contributor.author","Lühder, Fred"],["dc.contributor.author","Reichardt, Holger M."],["dc.date.accessioned","2019-07-10T08:13:33Z"],["dc.date.available","2019-07-10T08:13:33Z"],["dc.date.issued","2008"],["dc.description.abstract","High-dose glucocorticoid (GC) therapy is widely used to treat multiple sclerosis (MS), but the underlying mechanisms remain debatable. In this study, we investigated the impact of GC administration on experimental autoimmune encephalomyelitis using different GC receptor (GR)-deficient mutants. Heterozygous GR knockout mice were less sensitive to dexamethasone therapy, indicating that the expression level of the receptor determines therapeutic efficacy. Mice reconstituted with homozygous GR knockout fetal liver cells showed an earlier onset of the disease and were largely refractory to GC treatment, indicating that the GR in hematopoietic cells is essential for the beneficial effects of endogenous GCs and dexamethasone. Using cell-type specific GR-deficient mice, we could demonstrate that GCs mainly act on T cells, while modulation of macrophage function was largely dispensable in this context. The therapeutic effects were achieved through induction of apoptosis and down-regulation of cell adhesion molecules in peripheral T(H)17 and bystander T cells, while similar effects were not observed within the spinal cord. In addition, dexamethasone inhibited T cell migration into the CNS, confirming that peripheral but not CNS-residing T lymphocytes are the essential targets of GCs. Collectively, our findings reveal a highly selective mechanism of GC action in experimental autoimmune encephalomyelitis and presumably multiple sclerosis."],["dc.identifier.pmid","18523311"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6206"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61275"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","0022-1767"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","Goescholar"],["dc.subject.ddc","610"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Apoptosis"],["dc.subject.mesh","Blood-Brain Barrier"],["dc.subject.mesh","Cell Movement"],["dc.subject.mesh","Dexamethasone"],["dc.subject.mesh","Down-Regulation"],["dc.subject.mesh","Drug Delivery Systems"],["dc.subject.mesh","Encephalomyelitis, Autoimmune, Experimental"],["dc.subject.mesh","Female"],["dc.subject.mesh","Glycoproteins"],["dc.subject.mesh","Intercellular Signaling Peptides and Proteins"],["dc.subject.mesh","Leukocytes"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Mice, Inbred C57BL"],["dc.subject.mesh","Mice, Knockout"],["dc.subject.mesh","Mice, Transgenic"],["dc.subject.mesh","Peptide Fragments"],["dc.subject.mesh","Receptors, Glucocorticoid"],["dc.subject.mesh","T-Lymphocyte Subsets"],["dc.subject.mesh","T-Lymphocytes, Regulatory"],["dc.title","Peripheral T cells are the therapeutic targets of glucocorticoids in experimental autoimmune encephalomyelitis."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]