Simons, Mikael

[["dc.bibliographiccitation.firstpage","305"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Current Neuropharmacology"],["dc.bibliographiccitation.lastpage","315"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Fitzner, Dirk"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T08:39:36Z"],["dc.date.available","2018-11-07T08:39:36Z"],["dc.date.issued","2010"],["dc.description.abstract","Multiple sclerosis (MS) is an inflammatory, autoimmune, demyelinating disease of the central nervous system (CNS) that usually starts as a relapsing-remitting disease. In most patients the disease evolves into a chronic progressive phase characterized by continuous accumulation of neurological deficits. While treatment of relapsing-remitting MS (RRMS) has improved dramatically over the last decade, the therapeutic options for chronic progressive MS, both primary and secondary, are still limited. In order to find new pharmacological targets for the treatment of chronic progressive MS, the mechanisms of the underlying neurodegenerative process that becomes apparent as the disease progresses need to be elucidated. New animal models with prominent and widespread progressive degenerative components of MS have to be established to study both inflammatory and non-inflammatory mechanisms of neurodegeneration. Here, we discuss disease mechanisms and treatment strategies for chronic progressive MS."],["dc.description.sponsorship","ERC; EMBO"],["dc.identifier.isi","000281436200014"],["dc.identifier.pmid","21358979"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19037"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Bentham Science Publ Ltd"],["dc.relation.issn","1570-159X"],["dc.title","Chronic Progressive Multiple Sclerosis - Pathogenesis of Neurodegeneration and Therapeutic Strategies"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","447"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Cell Science"],["dc.bibliographiccitation.lastpage","458"],["dc.bibliographiccitation.volume","124"],["dc.contributor.author","Fitzner, Dirk"],["dc.contributor.author","Schnaars, Mareike"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Krishnamoorthy, Gurumoorthy"],["dc.contributor.author","Dibaj, Payam"],["dc.contributor.author","Bakhti, Mostafa"],["dc.contributor.author","Regen, Tommy"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T08:59:39Z"],["dc.date.available","2018-11-07T08:59:39Z"],["dc.date.issued","2011"],["dc.description.abstract","The transfer of antigens from oligodendrocytes to immune cells has been implicated in the pathogenesis of autoimmune diseases. Here, we show that oligodendrocytes secrete small membrane vesicles called exosomes, which are specifically and efficiently taken up by microglia both in vitro and in vivo. Internalisation of exosomes occurs by a macropinocytotic mechanism without inducing a concomitant inflammatory response. After stimulation of microglia with interferon-gamma, we observe an upregulation of MHC class II in a subpopulation of microglia. However, exosomes are preferentially internalised in microglia that do not seem to have antigen-presenting capacity. We propose that the constitutive macropinocytotic clearance of exosomes by a subset of microglia represents an important mechanism through which microglia participate in the degradation of oligodendroglial membrane in an immunologically 'silent' manner. By designating the capacity for macropinocytosis and antigen presentation to distinct cells, degradation and immune function might be assigned to different subtypes of microglia."],["dc.description.sponsorship","ERC; EMBO YIP; German Research Council [SFB/TR43]"],["dc.identifier.doi","10.1242/jcs.074088"],["dc.identifier.isi","000286223600016"],["dc.identifier.pmid","21242314"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8034"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23953"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Company Of Biologists Ltd"],["dc.relation.issn","0021-9533"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2461"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Annals of Clinical and Translational Neurology"],["dc.bibliographiccitation.lastpage","2466"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Penkert, Horst"],["dc.contributor.author","Lauber, Chris"],["dc.contributor.author","Gerl, Mathias J."],["dc.contributor.author","Klose, Christian"],["dc.contributor.author","Damm, Markus"],["dc.contributor.author","Fitzner, Dirk"],["dc.contributor.author","Flierl‐Hecht, Andrea"],["dc.contributor.author","Kümpfel, Tania"],["dc.contributor.author","Kerschensteiner, Martin"],["dc.contributor.author","Hohlfeld, Reinhard"],["dc.contributor.author","Gerdes, Lisa A."],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2021-04-14T08:32:24Z"],["dc.date.available","2021-04-14T08:32:24Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1002/acn3.51216"],["dc.identifier.pmid","33159711"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83910"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/1"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B01: The role of inflammatory cytokine signaling for efficient remyelination in multiple sclerosis"],["dc.relation","TRR 274 | C02: In vivo detection and targeting of calcium clearance and axonal membrane repair after acute CNS insults"],["dc.relation.issn","2328-9503"],["dc.relation.workinggroup","RG Kerschensteiner (Neuroimmune Interactions)"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","Plasma lipidomics of monozygotic twins discordant for multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","40"],["dc.bibliographiccitation.journal","BMC Neuroscience"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Kippert, Angelika"],["dc.contributor.author","Trajkovic, Katarina"],["dc.contributor.author","Fitzner, Dirk"],["dc.contributor.author","Opitz, Lennart"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T11:15:57Z"],["dc.date.available","2018-11-07T11:15:57Z"],["dc.date.issued","2008"],["dc.description.abstract","Background: During the development of the central nervous system, oligodendrocytes generate large amounts of myelin, a multilayered insulating membrane that ensheathes axons, thereby allowing the fast conduction of the action potential and maintaining axonal integrity. Differentiation of oligodendrocytes to myelin-forming cells requires the downregulation of RhoA GTPase activity. Results: To gain insights into the molecular mechanisms of oligodendrocyte differentiation, we performed microarray expression profiling of the oligodendroglial cell line, Oli-neu, treated with the Rho kinase ( ROCK) inhibitor, Y-27632 or with conditioned neuronal medium. This resulted in the identification of the transmembrane protein 10 ( Tmem10/Opalin), a novel type I transmembrane protein enriched in differentiating oligodendrocytes. In primary cultures, Tmem10 was abundantly expressed in O4-positive oligodendrocytes, but not in oligodendroglial precursor cells, astrocytes, microglia or neurons. In mature oligodendrocytes Tmem10 was enriched in the rims and processes of the cells and was only found to a lesser extent in the membrane sheets. Conclusion: Together, our results demonstrate that Tmem10 is a novel marker for in vitro generated oligodendrocytes."],["dc.identifier.doi","10.1186/1471-2202-9-40"],["dc.identifier.isi","000256221800001"],["dc.identifier.pmid","18439243"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11207"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/54484"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2202"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Identification of Tmem10/Opalin as a novel marker for oligodendrocytes using gene expression profiling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2127"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Development"],["dc.bibliographiccitation.lastpage","2132"],["dc.bibliographiccitation.volume","137"],["dc.contributor.author","Budde, Holger"],["dc.contributor.author","Schmitt, Sebastian"],["dc.contributor.author","Fitzner, Dirk"],["dc.contributor.author","Opitz, Lennart"],["dc.contributor.author","Salinas-Riester, Gabriela"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T08:41:36Z"],["dc.date.available","2018-11-07T08:41:36Z"],["dc.date.issued","2010"],["dc.description.abstract","The generation of myelinating cells in the central nervous system requires the initiation of specific gene expression programs in oligodendrocytes. We reasoned that microRNAs (miRNAs) could play an important role in this process by regulating crucial developmental genes. Microarray profiling of cultured oligodendrocytes identified the miR-17-92 miRNA cluster as highly enriched in oligodendrocytes. We specifically deleted the miR-17-92 cluster in oligodendrocytes using 2',3'-cyclic nucleotide 3' phosphodiesterase (Cnp)-Cre mice. Absence of miR-17-92 leads to a reduction in oligodendrocyte number in vivo and we find that the expression of these miRNAs in primary cultures of oligodendrocyte precursor cells promotes cell proliferation by influencing Akt signaling. Together, these results suggest that the miRNA pathway is essential in determining oligodendroglial cell number and that the miR-17-92 cluster is crucial in this process."],["dc.description.sponsorship","ERC; EMBO YIP; Boehringer Ingelheim Fonds"],["dc.identifier.doi","10.1242/dev.050633"],["dc.identifier.isi","000278559900006"],["dc.identifier.pmid","20504959"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/19507"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Company Of Biologists Ltd"],["dc.relation.issn","0950-1991"],["dc.title","Control of oligodendroglial cell number by the miR-17-92 cluster"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5037"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","5048"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Fitzner, Dirk"],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","Kippert, Angelika"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Willig, Katrin I."],["dc.contributor.author","Hell, Stefan"],["dc.contributor.author","Bunt, Gertrude"],["dc.contributor.author","Gaus, Katharina"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2017-09-07T11:52:27Z"],["dc.date.available","2017-09-07T11:52:27Z"],["dc.date.issued","2006"],["dc.description.abstract","During vertebrate development, oligodendrocytes wrap their plasma membrane around axons to produce myelin, a specialized membrane highly enriched in galactosylceramide (GalC) and cholesterol. Here, we studied the formation of myelin membrane sheets in a neuron-glia co-culture system. We applied different microscopy techniques to visualize lipid packing and dynamics in the oligodendroglial plasma membrane. We used the fluorescent dye Laurdan to examine the lipid order with two-photon microscopy and observed that neurons induce a dramatic lipid condensation of the oligodendroglial membrane. On a nanoscale resolution, using stimulated emission depletion and fluorescence resonance energy transfer microscopy, we demonstrated a neuronal-dependent clustering of GalC in oligodendrocytes. Most importantly these changes in lipid organization of the oligodendroglial plasma membrane were not observed in shiverer mice that do not express the myelin basic protein. Our data demonstrate that neurons induce the condensation of the myelin-forming bilayer in oligodendrocytes and that MBP is involved in this process of plasma membrane rearrangement. We propose that this mechanism is essential for myelin to perform its insulating function during nerve conduction."],["dc.identifier.doi","10.1038/sj.emboj.7601376"],["dc.identifier.gro","3143596"],["dc.identifier.isi","000242214900001"],["dc.identifier.pmid","17036049"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1128"],["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","0261-4189"],["dc.title","Myelin basic protein-dependent plasma membrane reorganization in the formation of myelin"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1116"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY"],["dc.bibliographiccitation.lastpage","1123"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Sun, Xingwen"],["dc.contributor.author","Bakhti, Mostafa"],["dc.contributor.author","Fitzner, Dirk"],["dc.contributor.author","Schnaars, Mareike"],["dc.contributor.author","Kruse, Niels"],["dc.contributor.author","Coskun, Uenal"],["dc.contributor.author","Kremser, Christiane"],["dc.contributor.author","Willecke, Klaus"],["dc.contributor.author","Kappos, Ludwig"],["dc.contributor.author","Kuhle, Jens"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T09:48:10Z"],["dc.date.available","2018-11-07T09:48:10Z"],["dc.date.issued","2015"],["dc.description.abstract","Background: Synthesis of clonal IgG is a consistent feature of patients with multiple sclerosis (MS). Whether oligoclonal bands (OCBs) represent unspecific disease bystanders or active components in MS pathology is an open question. The aim of this study was to develop a method to quantify and compare the reactivity of cerebrospinal fluid (CSF) antibodies from patients with and without MS. Methods: We collected CSF from 262 patients from two different cohorts, which included 148 patients with MS and 114 with other neurological diseases (OND). We established a highly sensitive electrochemiluminescence (ECL)-based assay to measure CSF antibody reactivity against purified myelin particles and biotin anchored liposomes. The diagnostic value of the ECL score against myelin particles was assessed with receiver operating characteristic curves. Results: CSF from patients with MS have higher reactivity toward purified myelin particles as compared to those with OND with OCBs. Using liposomes with defined lipid compositions and myelin particles from ceramide synthase 2 (CerS2) knockout mice, we find that some of the CSF antibody reactivity is directed against cerebrosides. Conclusion: The ECL-based assay system expands the currently available toolbox for the detection of autoantibodies in MS and related diseases."],["dc.identifier.doi","10.1002/acn3.264"],["dc.identifier.isi","000367240500006"],["dc.identifier.pmid","26734662"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35253"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","2328-9503"],["dc.title","Quantified CSF antibody reactivity against myelin in multiple sclerosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","684"],["dc.bibliographiccitation.issue","6376"],["dc.bibliographiccitation.journal","Science"],["dc.bibliographiccitation.lastpage","688"],["dc.bibliographiccitation.volume","359"],["dc.contributor.author","Cantuti-Castelvetri, Ludovico"],["dc.contributor.author","Fitzner, Dirk"],["dc.contributor.author","Bosch-Queralt, Mar"],["dc.contributor.author","Weil, Marie-Theres"],["dc.contributor.author","Su, Minhui"],["dc.contributor.author","Sen, Paromita"],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Mitkovski, Miso"],["dc.contributor.author","Trendelenburg, George"],["dc.contributor.author","Lütjohann, Dieter"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2020-12-10T18:36:42Z"],["dc.date.available","2020-12-10T18:36:42Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1126/science.aan4183"],["dc.identifier.eissn","1095-9203"],["dc.identifier.issn","0036-8075"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/76715"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Defective cholesterol clearance limits remyelination in the aged central nervous system"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","108132"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Fitzner, Dirk"],["dc.contributor.author","Bader, Jakob M."],["dc.contributor.author","Penkert, Horst"],["dc.contributor.author","Bergner, Caroline G."],["dc.contributor.author","Su, Minhui"],["dc.contributor.author","Weil, Marie-Theres"],["dc.contributor.author","Surma, Michal A."],["dc.contributor.author","Mann, Matthias"],["dc.contributor.author","Klose, Christian"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2021-04-14T08:23:31Z"],["dc.date.available","2021-04-14T08:23:31Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1016/j.celrep.2020.108132"],["dc.identifier.pmid","32937123"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80949"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/23"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation","TRR 274 | B01: The role of inflammatory cytokine signaling for efficient remyelination in multiple sclerosis"],["dc.relation.issn","2211-1247"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","Cell-Type- and Brain-Region-Resolved Mouse Brain Lipidome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","71"],["dc.bibliographiccitation.journal","BMC Cell Biology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Kippert, Angelika"],["dc.contributor.author","Fitzner, Dirk"],["dc.contributor.author","Helenius, Jonne"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T11:24:12Z"],["dc.date.available","2018-11-07T11:24:12Z"],["dc.date.issued","2009"],["dc.description.abstract","Background: To form myelin oligodendrocytes expand and wrap their plasma membrane multiple times around an axon. How is this expansion controlled? Results: Here we show that cell surface area depends on actomyosin contractility and is regulated by physical properties of the supporting matrix. Moreover, we find that chondroitin sulfate proteoglycans (CSPG), molecules associated with non-permissive growth properties within the central nervous system (CNS), block cell surface spreading. Most importantly, the inhibitory effects of CSPG on plasma membrane extension were completely prevented by treatment with inhibitors of actomyosin contractility and by RNAi mediated knockdown of myosin II. In addition, we found that reductions of plasma membrane area were accompanied by changes in the rate of fluid-phase endocytosis. Conclusion: In summary, our results establish a novel connection between endocytosis, cell surface extension and actomyosin contractility. These findings open up new possibilities of how to promote the morphological differentiation of oligodendrocytes in a non-permissive growth environment."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [SFB 523]; ERC Starting; EMBO YIP"],["dc.identifier.doi","10.1186/1471-2121-10-71"],["dc.identifier.isi","000271203700001"],["dc.identifier.pmid","19781079"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5787"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56349"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1471-2121"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Actomyosin contractility controls cell surface area of oligodendrocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]