Simons, Mikael

[["dc.bibliographiccitation.artnumber","13275"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Romanelli, Elisa"],["dc.contributor.author","Merkler, Doron"],["dc.contributor.author","Mezydlo, Aleksandra"],["dc.contributor.author","Weil, Marie-Theres"],["dc.contributor.author","Weber, Martin S."],["dc.contributor.author","Nikic, Ivana"],["dc.contributor.author","Potz, Stephanie"],["dc.contributor.author","Meinl, Edgar"],["dc.contributor.author","Matznick, Florian E. H."],["dc.contributor.author","Kreutzfeldt, Mario"],["dc.contributor.author","Ghanem, Alexander"],["dc.contributor.author","Conzelmann, Karl-Klaus"],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Routh, Matthew"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Bishop, Derron"],["dc.contributor.author","Misgeld, Thomas"],["dc.contributor.author","Kerschensteiner, Martin"],["dc.date.accessioned","2018-11-07T10:05:43Z"],["dc.date.available","2018-11-07T10:05:43Z"],["dc.date.issued","2016"],["dc.description.abstract","Oligodendrocyte damage is a central event in the pathogenesis of the common neuro-inflammatory condition, multiple sclerosis (MS). Where and how oligodendrocyte damage is initiated in MS is not completely understood. Here, we use a combination of light and electron microscopy techniques to provide a dynamic and highly resolved view of oligodendrocyte damage in neuroinflammatory lesions. We show that both in MS and in its animal model structural damage is initiated at the myelin sheaths and only later spreads to the oligodendrocyte cell body. Early myelin damage itself is characterized by the formation of local myelin out-foldings-'myelinosomes'-, which are surrounded by phagocyte processes and promoted in their formation by anti-myelin antibodies and complement. The presence of myelinosomes in actively demyelinating MS lesions suggests that oligodendrocyte damage follows a similar pattern in the human disease, where targeting demyelination by therapeutic interventions remains a major open challenge."],["dc.identifier.doi","10.1038/ncomms13275"],["dc.identifier.isi","000387837900001"],["dc.identifier.pmid","27848954"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13963"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38953"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2041-1723"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Myelinosome formation represents an early stage of oligodendrocyte damage in multiple sclerosis and its animal model"],["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.artnumber","e1001577"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","PLoS Biology"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Aggarwal, Shweta"],["dc.contributor.author","Snaidero, Nicolas"],["dc.contributor.author","Paehler, Gesa"],["dc.contributor.author","Frey, Steffen"],["dc.contributor.author","Sanchez, Paula"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Janshoff, Andreas"],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","Weil, Marie-Theres"],["dc.contributor.author","Schaap, Iwan Alexander Taco"],["dc.contributor.author","Goerlich, Dirk"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T09:23:52Z"],["dc.date.available","2018-11-07T09:23:52Z"],["dc.date.issued","2013"],["dc.description.abstract","Rapid conduction of nerve impulses requires coating of axons by myelin. To function as an electrical insulator, myelin is generated as a tightly packed, lipid-rich multilayered membrane sheath. Knowledge about the mechanisms that govern myelin membrane biogenesis is required to understand myelin disassembly as it occurs in diseases such as multiple sclerosis. Here, we show that myelin basic protein drives myelin biogenesis using weak forces arising from its inherent capacity to phase separate. The association of myelin basic protein molecules to the inner leaflet of the membrane bilayer induces a phase transition into a cohesive mesh-like protein network. The formation of this protein network shares features with amyloid fibril formation. The process is driven by phenylalanine-mediated hydrophobic and amyloid-like interactions that provide the molecular basis for protein extrusion and myelin membrane zippering. These findings uncover a physicochemical mechanism of how a cytosolic protein regulates the morphology of a complex membrane architecture. These results provide a key mechanism in myelin membrane biogenesis with implications for disabling demyelinating diseases of the central nervous system."],["dc.description.sponsorship","ERC Starting Grant; German Research Foundation [SI 746/9-1, TRR43]"],["dc.identifier.doi","10.1371/journal.pbio.1001577"],["dc.identifier.fs","600727"],["dc.identifier.isi","000321042900005"],["dc.identifier.pmid","23762018"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9108"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29688"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1545-7885"],["dc.relation.orgunit","Fakultät für Physik"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","http://creativecommons.org/licenses/by-nc-nd/3.0/"],["dc.title","Myelin Membrane Assembly Is Driven by a Phase Transition of Myelin Basic Proteins Into a Cohesive Protein Meshwork"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","314"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.lastpage","322"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Weil, Marie-Theres"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Winkler, Anne"],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Wrzos, Claudia"],["dc.contributor.author","Romanelli, Elisa"],["dc.contributor.author","Bennett, Jeffrey L."],["dc.contributor.author","Enz, Lukas"],["dc.contributor.author","Goebels, Norbert"],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Kerschensteiner, Martin"],["dc.contributor.author","Schaeren-Wiemers, Nicole"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T10:11:38Z"],["dc.date.available","2018-11-07T10:11:38Z"],["dc.date.issued","2016"],["dc.description.abstract","Breakdown of myelin sheaths is a pathological hallmark of several autoimmune diseases of the nervous system. We employed autoantibody-mediated animal models of demyelinating diseases, including a rat model of neuromyelitis optica (NMO), to target myelin and found that myelin lamellae are broken down into vesicular structures at the innermost region of the myelin sheath. We demonstrated that myelin basic proteins (MBP), which form a polymer in between the myelin membrane layers, are targeted in these models. Elevation of intracellular Ca2+ levels resulted in MBP network disassembly and myelin vesiculation. We propose that the aberrant phase transition of MBP molecules from their cohesive to soluble and non-adhesive state is a mechanism triggering myelin breakdown in NMO and possibly in other demyelinating diseases."],["dc.identifier.doi","10.1016/j.celrep.2016.06.008"],["dc.identifier.isi","000380262300005"],["dc.identifier.pmid","27346352"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13675"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40088"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cell Press"],["dc.relation.issn","2211-1247"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases"],["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.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Djannatian, Minou"],["dc.contributor.author","Timmler, Sebastian"],["dc.contributor.author","Arends, Martina"],["dc.contributor.author","Luckner, Manja"],["dc.contributor.author","Weil, Marie-Theres"],["dc.contributor.author","Alexopoulos, Ioannis"],["dc.contributor.author","Snaidero, Nicolas"],["dc.contributor.author","Schmid, Bettina"],["dc.contributor.author","Misgeld, Thomas"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Schifferer, Martina"],["dc.contributor.author","Peles, Elior"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2019-11-14T10:54:01Z"],["dc.date.accessioned","2021-10-27T13:21:27Z"],["dc.date.available","2019-11-14T10:54:01Z"],["dc.date.available","2021-10-27T13:21:27Z"],["dc.date.issued","2019"],["dc.description.abstract","Central nervous system myelin is a multilayered membrane produced by oligodendrocytes to increase neural processing speed and efficiency, but the molecular mechanisms underlying axonal selection and myelin wrapping are unknown. Here, using combined morphological and molecular analyses in mice and zebrafish, we show that adhesion molecules of the paranodal and the internodal segment work synergistically using overlapping functions to regulate axonal interaction and myelin wrapping. In the absence of these adhesive systems, axonal recognition by myelin is impaired with myelin growing on top of previously myelinated fibers, around neuronal cell bodies and above nodes of Ranvier. In addition, myelin wrapping is disturbed with the leading edge moving away from the axon and in between previously formed layers. These data show how two adhesive systems function together to guide axonal ensheathment and myelin wrapping, and provide a mechanistic understanding of how the spatial organization of myelin is achieved."],["dc.identifier.doi","10.1038/s41467-019-12789-z"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16665"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92023"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","2041-1723"],["dc.relation.issn","2041-1723"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject.ddc","573"],["dc.subject.ddc","612"],["dc.title","Two adhesive systems cooperatively regulate axon ensheathment and myelin growth in the CNS"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]