Winkler, Anne

[["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.journal","Brain"],["dc.contributor.author","Herwerth, Marina"],["dc.contributor.author","Kenet, Selin"],["dc.contributor.author","Schifferer, Martina"],["dc.contributor.author","Winkler, Anne"],["dc.contributor.author","Weber, Melanie"],["dc.contributor.author","Snaidero, Nicolas"],["dc.contributor.author","Wang, Mengzhe"],["dc.contributor.author","Lohrberg, Melanie"],["dc.contributor.author","Bennett, Jeffrey L."],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Misgeld, Thomas"],["dc.date.accessioned","2022-04-01T10:02:49Z"],["dc.date.available","2022-04-01T10:02:49Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract Neuromyelitis optica (NMO) is a chronic neuroinflammatory disease, which primarily targets astrocytes and often results in severe axon injury of unknown mechanism. NMO patients harbor autoantibodies against the astrocytic water channel protein, aquaporin-4 (AQP4-IgG), which induce complement-mediated astrocyte lysis and subsequent axon damage. Using spinal in vivo imaging in a mouse model of such astrocytopathic lesions, we explored the mechanism underlying NMO-related axon injury. Many axons showed a swift and morphologically distinct ‘pearls-on-string’ transformation also readily detectable in human NMO lesions, which especially affected small caliber axons independently of myelination. Functional imaging revealed that calcium homeostasis was initially preserved in this ‘acute axonal beading’ state, ruling out disruption of the axonal membrane, which sets this form of axon injury apart from previously described forms of traumatic and inflammatory axon damage. Morphological, pharmacological and genetic analyses showed that AQP4-IgG-induced axon injury involved osmotic stress and ionic overload, but does not appear to use canonical pathways of Wallerian-like degeneration. Subcellular analysis of beaded axons demonstrated remodeling of the axonal cytoskeleton in beaded axons, especially local loss of microtubules. Treatment with the microtubule stabilizer epothilone, a therapy in development for traumatic and degenerative axonopathies, prevented axonal beading, while destabilizing microtubules sensitized axons for beading. Our results reveal a distinct form of immune-mediated axon pathology in NMO that mechanistically differs from known cascades of posttraumatic and inflammatory axon loss, and suggest a new strategy for neuroprotection in NMO and related diseases."],["dc.identifier.doi","10.1093/brain/awac079"],["dc.identifier.pmid","35202467"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/106013"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/454"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/59"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation.eissn","1460-2156"],["dc.relation.issn","0006-8950"],["dc.relation.workinggroup","RG Stadelmann-Nessler"],["dc.relation.workinggroup","RG Misgeld"],["dc.relation.workinggroup","RG Schifferer"],["dc.rights","CC BY-NC 4.0"],["dc.title","A new form of axonal pathology in a spinal model of neuromyelitis optica"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]