Möbius, Wiebke

[["dc.bibliographiccitation.firstpage","567"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","586"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Kraemer-Albers, Eva-Maria"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Saher, Gesine"],["dc.contributor.author","Tenzer, Stefan"],["dc.contributor.author","Ohno-Iwashita, Yoshiko"],["dc.contributor.author","Monasterio-Schrader, Patricia de"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Griffiths, Ian R."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.date.accessioned","2017-09-07T11:47:44Z"],["dc.date.available","2017-09-07T11:47:44Z"],["dc.date.issued","2013"],["dc.description.abstract","The formation of central nervous system myelin by oligodendrocytes requires sterol synthesis and is associated with a significant enrichment of cholesterol in the myelin membrane. However, it is unknown how oligodendrocytes concentrate cholesterol above the level found in nonmyelin membranes. Here, we demonstrate a critical role for proteolipids in cholesterol accumulation. Mice lacking the most abundant myelin protein, proteolipid protein (PLP), are fully myelinated, but PLP-deficient myelin exhibits a reduced cholesterol content. We therefore hypothesized that high cholesterol is not essential in the myelin sheath itself but is required for an earlier step of myelin biogenesis that is fully compensated for in the absence of PLP. We also found that a PLP-homolog, glycoprotein M6B, is a myelin component of low abundance. By targeting the Gpm6b-gene and crossbreeding, we found that single-mutant mice lacking either PLP or M6B are fully myelinated, while double mutants remain severely hypomyelinated, with enhanced neurodegeneration and premature death. As both PLP and M6B bind membrane cholesterol and associate with the same cholesterol-rich oligodendroglial membrane microdomains, we suggest a model in which proteolipids facilitate myelination by sequestering cholesterol. While either proteolipid can maintain a threshold level of cholesterol in the secretory pathway that allows myelin biogenesis, lack of both proteolipids results in a severe molecular imbalance of prospective myelin membrane. However, M6B is not efficiently sorted into mature myelin, in which it is 200-fold less abundant than PLP. Thus, only PLP contributes to the high cholesterol content of myelin by association and co-transport. (c) 2013 Wiley Periodicals, Inc."],["dc.identifier.doi","10.1002/glia.22456"],["dc.identifier.gro","3142368"],["dc.identifier.isi","000314981400010"],["dc.identifier.pmid","23322581"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7508"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: BMBF; European Commission"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0894-1491"],["dc.title","A critical role for the cholesterol-associated proteolipids PLP and M6B in myelination of the central nervous system"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","47"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Neuroscience"],["dc.bibliographiccitation.lastpage","60"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Berghoff, Stefan A."],["dc.contributor.author","Spieth, Lena"],["dc.contributor.author","Sun, Ting"],["dc.contributor.author","Hosang, Leon"],["dc.contributor.author","Schlaphoff, Lennart"],["dc.contributor.author","Depp, Constanze"],["dc.contributor.author","Düking, Tim"],["dc.contributor.author","Winchenbach, Jan"],["dc.contributor.author","Neuber, Jonathan"],["dc.contributor.author","Ewers, David"],["dc.contributor.author","Scholz, Patricia"],["dc.contributor.author","van der Meer, Franziska"],["dc.contributor.author","Cantuti-Castelvetri, Ludovico"],["dc.contributor.author","Sasmita, Andrew O."],["dc.contributor.author","Meschkat, Martin"],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Sankowski, Roman"],["dc.contributor.author","Prinz, Marco"],["dc.contributor.author","Huitinga, Inge"],["dc.contributor.author","Sereda, Michael W."],["dc.contributor.author","Odoardi, Francesca"],["dc.contributor.author","Ischebeck, Till"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Stadelmann-Nessler, Christine"],["dc.contributor.author","Edgar, Julia M."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Saher, Gesine"],["dc.date.accessioned","2021-04-14T08:27:05Z"],["dc.date.available","2021-04-14T08:27:05Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1038/s41593-020-00757-6"],["dc.identifier.pmid","33349711"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82162"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/11"],["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 | A04: The role of the meninges in the resolution of acute autoimmune CNS lesions"],["dc.relation.eissn","1546-1726"],["dc.relation.issn","1097-6256"],["dc.relation.workinggroup","RG Cantuti"],["dc.relation.workinggroup","RG Nave (Neurogenetics)"],["dc.relation.workinggroup","RG Odoardi (Echtzeitdarstellung neuroimmunologischer Prozesse)"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.relation.workinggroup","RG Stadelmann-Nessler"],["dc.title","Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2205"],["dc.bibliographiccitation.issue","14"],["dc.bibliographiccitation.journal","FEBS Letters"],["dc.bibliographiccitation.lastpage","2211"],["dc.bibliographiccitation.volume","585"],["dc.contributor.author","Kassmann, Celia M."],["dc.contributor.author","Quintes, Susanne"],["dc.contributor.author","Rietdorf, Jens"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Sereda, Michael Werner"],["dc.contributor.author","Nientiedt, Tobias"],["dc.contributor.author","Saher, Gesine"],["dc.contributor.author","Baes, Myriam"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.date.accessioned","2022-03-01T11:45:09Z"],["dc.date.available","2022-03-01T11:45:09Z"],["dc.date.issued","2011"],["dc.identifier.doi","10.1016/j.febslet.2011.05.032"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103228"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0014-5793"],["dc.title","A role for myelin-associated peroxisomes in maintaining paranodal loops and axonal integrity"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","S115"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","S116"],["dc.bibliographiccitation.volume","57"],["dc.contributor.author","de Monasterio-Schrader, P."],["dc.contributor.author","Werner, Hauke B."],["dc.contributor.author","Kraemer-Albers, Eva-Maria"],["dc.contributor.author","Strenzke, Nicola"],["dc.contributor.author","Saher, Gesine"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Tenzer, S."],["dc.contributor.author","Ohno-Iwashita, Y."],["dc.contributor.author","Moser, Tobias"],["dc.contributor.author","Griffiths, I. R."],["dc.contributor.author","Nave, K. A."],["dc.date.accessioned","2018-11-07T11:23:39Z"],["dc.date.available","2018-11-07T11:23:39Z"],["dc.date.issued","2009"],["dc.identifier.isi","000270075500479"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56236"],["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","High-Level Expression of the Proteolipids Plp and M6b is Sufficient to Induce Oligodendroglial Process Outgrowth in Vitro and Required for Normal Myelination in Vivo"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1130"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Nature Medicine"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Saher, Gesine"],["dc.contributor.author","Rudolphi, Fabian"],["dc.contributor.author","Corthals, Kristina"],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Schmidt, Karl-Friedrich"],["dc.contributor.author","Loewel, Siegrid"],["dc.contributor.author","Dibaj, Payam"],["dc.contributor.author","Barrette, Benoit"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.date.accessioned","2018-11-07T09:08:43Z"],["dc.date.available","2018-11-07T09:08:43Z"],["dc.date.issued","2012"],["dc.description.abstract","Duplication of PLP1 (proteolipid protein gene 1) and the subsequent overexpression of the myelin protein PLP (also known as DM20) in oligodendrocytes is the most frequent cause of Pelizaeus-Merzbacher disease (PMD), a fatal leukodystrophy(1) without therapeutic options(2,3). PLP binds cholesterol and is contained within membrane lipid raft microdomains(4). Cholesterol availability is the rate-limiting factor of central nervous system myelin synthesis(5). Transgenic mice with extra copies of the Plp1 gene(6) are accurate models of PMD. Dysmyelination(6-8) followed by demyelination(9,10), secondary inflammation and axon damage contribute to the severe motor impairment in these mice(9,10). The finding that in Plp1-transgenic oligodendrocytes, PLP and cholesterol accumulate in late endosomes and lysosomes (endo/lysosomes)(9,11-13), prompted us to further investigate the role of cholesterol in PMD. Here we show that cholesterol itself promotes normal PLP trafficking and that dietary cholesterol influences PMD pathology. In a preclinical trial, PMD mice were fed a cholesterol-enriched diet. This restored oligodendrocyte numbers and ameliorated intracellular PLP accumulation. Moreover, myelin content increased, inflammation and gliosis were reduced and motor defects improved. Even after onset of clinical symptoms, cholesterol treatment prevented disease progression. Dietary cholesterol did not reduce Plp1 overexpression but facilitated incorporation of PLP into myelin membranes. These findings may have implications for therapeutic interventions in patients with PMD."],["dc.identifier.doi","10.1038/nm.2833"],["dc.identifier.isi","000306121600044"],["dc.identifier.pmid","22706386"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26092"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1078-8956"],["dc.title","Therapy of Pelizaeus-Merzbacher disease in mice by feeding a cholesterol-enriched diet"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","468"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Nature Neuroscience"],["dc.bibliographiccitation.lastpage","475"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Saher, Gesine"],["dc.contributor.author","Brügger, Britta"],["dc.contributor.author","Lappe-Siefke, Corinna"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Tozawa, Ryu-ichi"],["dc.contributor.author","Wehr, Michael C"],["dc.contributor.author","Wieland, Felix"],["dc.contributor.author","Ishibashi, Shun"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.date.accessioned","2021-06-01T10:50:36Z"],["dc.date.available","2021-06-01T10:50:36Z"],["dc.date.issued","2005"],["dc.identifier.doi","10.1038/nn1426"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86717"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation.eissn","1546-1726"],["dc.relation.issn","1097-6256"],["dc.title","High cholesterol level is essential for myelin membrane growth"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]