Simons, Mikael

[["dc.bibliographiccitation.firstpage","277"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Cell"],["dc.bibliographiccitation.lastpage","290"],["dc.bibliographiccitation.volume","156"],["dc.contributor.author","Snaidero, Nicolas"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Czopka, Tim"],["dc.contributor.author","Hekking, Liesbeth H. P."],["dc.contributor.author","Mathisen, Cliff"],["dc.contributor.author","Verkleij, Dick"],["dc.contributor.author","Goebbels, Sandra"],["dc.contributor.author","Edgar, Julia M."],["dc.contributor.author","Merkler, Doron"],["dc.contributor.author","Lyons, David A."],["dc.contributor.author","Nave, Klaus-Armin"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T09:45:05Z"],["dc.date.available","2018-11-07T09:45:05Z"],["dc.date.issued","2014"],["dc.description.abstract","Central nervous system myelin is a multilayered membrane sheath generated by oligodendrocytes for rapid impulse propagation. However, the underlying mechanisms of myelin wrapping have remained unclear. Using an integrative approach of live imaging, electron microscopy, and genetics, we show that new myelin membranes are incorporated adjacent to the axon at the innermost tongue. Simultaneously, newly formed layers extend laterally, ultimately leading to the formation of a set of closely apposed paranodal loops. An elaborated system of cytoplasmic channels within the growing myelin sheath enables membrane trafficking to the leading edge. Most of these channels close with ongoing development but can be reopened in adults by experimentally raising phosphatidylinositol-(3,4,5)-triphosphate levels, which reinitiates myelin growth. Our model can explain assembly of myelin as a multilayered structure, abnormal myelin outfoldings in neurological disease, and plasticity of myelin biogenesis observed in adult life."],["dc.identifier.doi","10.1016/j.cell.2013.11.044"],["dc.identifier.isi","000329912200027"],["dc.identifier.pmid","24439382"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34540"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cell Press"],["dc.relation.issn","1097-4172"],["dc.relation.issn","0092-8674"],["dc.title","Myelin Membrane Wrapping of CNS Axons by PI(3,4,5) P3-Dependent Polarized Growth at the Inner Tongue"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","512"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Current Opinion in Cell Biology"],["dc.bibliographiccitation.lastpage","519"],["dc.bibliographiccitation.volume","25"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Lyons, David A."],["dc.date.accessioned","2018-11-07T09:21:50Z"],["dc.date.available","2018-11-07T09:21:50Z"],["dc.date.issued","2013"],["dc.description.abstract","The formation of myelin in the central nervous system is a multistep process that involves coordinated cell cell interactions and dramatic changes in plasma membrane architecture. First, oligodendrocytes send our numerous highly ramified processes to sample the axonal environment and decide which axon(s) to select for myelination. After this decision is made and individual axon to oligodendrocyte contact has been established, the exploratory process of the oligodendrocyte is converted into a flat sheath that spreads and winds along and around its associated axon to generate a multilayered membrane stack. By compaction of the opposing extracellular layers of membrane and extrusion of almost all cytoplasm from the intracellular domain of the sheath, the characteristic membrane-rich multi-lamellar structure of myelin is formed. Here we highlight recent advances in identifying biophysical and signalling based mechanisms that are involved in axonal selection and myelin sheath generation by oligodendrocytes. A thorough understanding of the mechanisms underlying these events is a prerequisite for the design of novel myelin repair strategies in demyelinating and dysmyelinating diseases."],["dc.identifier.doi","10.1016/j.ceb.2013.04.007"],["dc.identifier.isi","000323084700017"],["dc.identifier.pmid","23707197"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29201"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Current Biology Ltd"],["dc.relation.issn","0955-0674"],["dc.title","Axonal selection and myelin sheath generation in the central nervous system"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","937"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","The Journal of Cell Biology"],["dc.bibliographiccitation.lastpage","948"],["dc.bibliographiccitation.volume","172"],["dc.contributor.author","Trajkovic, K."],["dc.contributor.author","Dhaunchak, A. S."],["dc.contributor.author","Goncalves, J. T."],["dc.contributor.author","Wenzel, D."],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","Bunt, Gertrude"],["dc.contributor.author","Nave, K. A."],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T10:06:22Z"],["dc.date.available","2018-11-07T10:06:22Z"],["dc.date.issued","2006"],["dc.description.abstract","During vertebrate brain development, axons are enwrapped by myelin, an insulating membrane produced by oligodendrocytes. Neuron-derived signaling molecules are temporally and spatially required to coordinate oligodendrocyte differentiation. In this study, we show that neurons regulate myelin membrane trafficking in oligodendrocytes. In the absence of neurons, the major myelin membrane protein, the proteolipid protein (PLP), is internalized and stored in late endosomes/lysosomes (LEs/Ls) by a cholesterol-dependent and clathrin-independent endocytosis pathway that requires actin and the RhoA guanosine triphosphatase. Upon maturation, the rate of endocytosis is reduced, and a cAMP-dependent neuronal signal triggers the transport of PLP from LEs/Ls to the plasma membrane. These findings reveal a fundamental and novel role of LEs/Ls in oligodendrocytes: to store and release PLP in a regulated fashion. The release of myelin membrane from LEs/Ls by neuronal signals may represent a mechanism to control myelin membrane growth."],["dc.identifier.doi","10.1083/jcb.200509022"],["dc.identifier.isi","000235971900018"],["dc.identifier.pmid","16520383"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39080"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Rockefeller Univ Press"],["dc.relation.issn","0021-9525"],["dc.title","Neuron to glia signaling triggers myelin membrane exocytosis from endosomal storage sites"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.contributor.author","Djannatian, Minou"],["dc.contributor.author","Weikert, Ulrich"],["dc.contributor.author","Safaiyan, Shima"],["dc.contributor.author","Wrede, Christoph"],["dc.contributor.author","Deichsel, Cassandra"],["dc.contributor.author","Kislinger, Georg"],["dc.contributor.author","Ruhwedel, Torben"],["dc.contributor.author","Campbell, Douglas S."],["dc.contributor.author","van Ham, Tjakko"],["dc.contributor.author","Schmid, Bettina"],["dc.contributor.author","Hegermann, Jan"],["dc.contributor.author","Möbius, Wiebke"],["dc.contributor.author","Schifferer, Martina"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2022-08-19T08:17:44Z"],["dc.date.available","2022-08-19T08:17:44Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1101/2021.02.02.429485"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113031"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/14"],["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.workinggroup","RG Schifferer"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","Myelin biogenesis is associated with pathological ultrastructure that is resolved by microglia during development"],["dc.type","preprint"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","132"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Cell Biology"],["dc.bibliographiccitation.lastpage","+"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Baskin, Jeremy M."],["dc.contributor.author","Wu, X."],["dc.contributor.author","Christiano, Romain"],["dc.contributor.author","Oh, Michael S."],["dc.contributor.author","Schauder, Curtis M."],["dc.contributor.author","Gazzerro, Elisabetta"],["dc.contributor.author","Messa, Mirko"],["dc.contributor.author","Baldassari, Simona"],["dc.contributor.author","Assereto, Stefania"],["dc.contributor.author","Biancheri, Roberta"],["dc.contributor.author","Zara, Federico"],["dc.contributor.author","Minetti, Carlo"],["dc.contributor.author","Raimondi, Andrea"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Walther, Tobias C."],["dc.contributor.author","Reinisch, Karin M."],["dc.contributor.author","De Camilli, Pietro"],["dc.date.accessioned","2018-11-07T10:21:43Z"],["dc.date.available","2018-11-07T10:21:43Z"],["dc.date.issued","2016"],["dc.description.abstract","Genetic defects in myelin formation and maintenance cause leukodystrophies, a group of white matter diseases whose mechanistic underpinnings are poorly understood(1,2). Hypomyelination and congenital cataract (HCC), one of these disorders, is caused by mutations in FAM126A, a gene of unknown function(3). We show that FAM126A, also known as hyccin, regulates the synthesis of phosphatidylinositol 4-phosphate (PtdIns(4)P), a determinant of plasma membrane identity(4-6). HCC patient fibroblasts exhibit reduced PtdIns(4)P levels. FAM126A is an intrinsic component of the plasma membrane phosphatidylinositol 4-kinase complex that comprises PI4KIII alpha and its adaptors TTC7 and EFR3 (refs 5,7). A FAM126A TTC7 alpha-crystal structure reveals an all-alpha-helical heterodimer with a large protein protein interface and a conserved surface that may mediate binding to PI4KIII alpha. Absence of FAM126A, the predominant FAM126 isoform in oligodendrocytes, destabilizes the PI4KIII alpha complex in mouse brain and patient fibroblasts. We propose that HCC pathogenesis involves defects in PtdIns(4)P production in oligodendrocytes, whose specialized function requires massive plasma membrane expansion and thus generation of PtdIns(4)P and downstream phosphoinositides(8-11). Our results point to a role for FAM126A in supporting myelination, an important process in development and also following acute exacerbations in multiple sclerosis(12-14)."],["dc.identifier.doi","10.1038/ncb3271"],["dc.identifier.isi","000367030900006"],["dc.identifier.pmid","26571211"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42143"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1476-4679"],["dc.relation.issn","1465-7392"],["dc.title","The leukodystrophy protein FAM126A (hyccin) regulates PtdIns(4)P synthesis at the plasma membrane"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","101141"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","STAR Protocols"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Bosch-Queralt, Mar"],["dc.contributor.author","Tiwari, Vini"],["dc.contributor.author","Damkou, Alkmini"],["dc.contributor.author","Vaculčiaková, Lenka"],["dc.contributor.author","Alexopoulos, Ioannis"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2022-08-19T07:37:21Z"],["dc.date.available","2022-08-19T07:37:21Z"],["dc.date.issued","2022"],["dc.description.abstract","Lysolecithin injections into the white matter tracts of the central nervous system are a valuable tool to study remyelination, but evaluating the resulting demyelinating lesion size is challenging. Here, we present a protocol to consistently measure the volume of demyelination and remyelination in mice following brain lysolecithin injections. We describe serial sectioning of the lesion, followed by the evaluation of the demyelinated area in two-dimensional images. We then detail the computation of the volume using our own automated iPython script. For complete details on the use and execution of this profile, please refer to Bosch-Queralt et al. (2021)."],["dc.identifier.doi","10.1016/j.xpro.2022.101141"],["dc.identifier.pmid","35141565"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113022"],["dc.identifier.url","https://rdp.sfb274.de/literature/publications/57"],["dc.language.iso","en"],["dc.relation","TRR 274: Checkpoints of Central Nervous System Recovery"],["dc.relation.eissn","2666-1667"],["dc.relation.workinggroup","RG Simons (The Biology of Glia in Development and Disease)"],["dc.title","A fluorescence microscopy-based protocol for volumetric measurement of lysolecithin lesion-associated de- and re-myelination in mouse brain"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["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","575"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Current Opinion in Cell Biology"],["dc.bibliographiccitation.lastpage","581"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Simons, Mikael"],["dc.contributor.author","Raposo, Graca"],["dc.date.accessioned","2018-11-07T11:25:55Z"],["dc.date.available","2018-11-07T11:25:55Z"],["dc.date.issued","2009"],["dc.description.abstract","Cells release different types of vesicular carriers of membrane and cytosolic components into the extracellular space. These vesicles are generated within the endosomal system or at the plasma membrane. Among the various kinds of secreted membrane vesicles, exosomes are vesicles with a diameter of 40-100 nm that are secreted upon fusion of multivesicular endosomes with the cell surface. Exosomes transfer not only membrane components but also nucleic acid between different cells, emphasizing their role in intercellular communication. This ability is likely to underlie the different physiological and pathological events, in which exosomes from different cell origins have been implicated. Only recently light have been shed on the subcellular compartments and mechanisms involved in their biogenesis and secretion opening new avenues to understand their functions."],["dc.description.sponsorship","ERC"],["dc.identifier.doi","10.1016/j.ceb.2009.03.007"],["dc.identifier.isi","000269243300014"],["dc.identifier.pmid","19442504"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56737"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Current Biology Ltd"],["dc.relation.issn","0955-0674"],["dc.title","Exosomes - vesicular carriers for intercellular communication"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","585"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Trends in Cell Biology"],["dc.bibliographiccitation.lastpage","593"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Aggarwal, Shweta"],["dc.contributor.author","Yurlova, Larisa"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T08:51:10Z"],["dc.date.available","2018-11-07T08:51:10Z"],["dc.date.issued","2011"],["dc.description.abstract","The wrapping of multiple layers of myelin membrane sheets around an axon is of fundamental importance for the function of the nervous system. In the central nervous system (CNS) oligodendrocytes synthesize tremendous amounts of cellular membrane to form multiple myelin internodes of highly stable membranes with a specific set of tightly packed lipids and proteins. In recent years, mouse mutants have allowed great advances in our understanding of the functional and structural role of many of the major components of myelin. The challenge now is to extend this knowledge to unravel the molecular machinery and mechanisms required to synthesize, assemble and wrap myelin multiple times around an axon at the appropriate developmental time. Such insight will be essential in designing new therapeutic strategies to promote remyelination in demyelinating disorders such as multiple sclerosis."],["dc.description.sponsorship","European Research Council; EMBO Young Investigator Program"],["dc.identifier.doi","10.1016/j.tcb.2011.06.004"],["dc.identifier.isi","000296002600005"],["dc.identifier.pmid","21763137"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21867"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science London"],["dc.relation.issn","0962-8924"],["dc.title","Central nervous system myelin: structure, synthesis and assembly"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","55833"],["dc.bibliographiccitation.issue","53"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","55839"],["dc.bibliographiccitation.volume","279"],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","Araújo, Gilda Wright"],["dc.contributor.author","Trajkovic, Katarina"],["dc.contributor.author","Herrmann, Martin M."],["dc.contributor.author","Merkler, Doron"],["dc.contributor.author","Mandelkow, Eva-Maria"],["dc.contributor.author","Weissert, Robert"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T10:43:09Z"],["dc.date.available","2018-11-07T10:43:09Z"],["dc.date.issued","2004"],["dc.description.abstract","Axonal damage is a major morphological correlate and cause of permanent neurological deficits in patients with multiple sclerosis (MS), a multifocal, inflammatory and demyelinating disease of the central nervous system. Hyperphosphorylation and pathological aggregation of microtubule-associated protein tau is a common feature of many neurodegenerative diseases with axonal degeneration including Alzheimer's disease. We have therefore analyzed tau phosphorylation, solubility and distribution in the brainstem of rats with experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Tau was hyperphosphorylated at several sites also phosphorylated in Alzheimer's disease and became partially detergent-insoluble in EAE brains. Morphological examination demonstrated accumulation of amorphous deposits of abnormally phosphorylated tau in the cell body and axons of neurons within demyelinating plaques. Hyperphosphorylation of tau was accompanied by up-regulation of p25, an activator of cyclin-dependent kinase 5. Phosphorylation of tau, activation of cdk5, and axonal pathology were significantly reduced when diseased rats were treated with prednisolone, a standard therapy of acute relapses in MS. Hyperphosphorylation of tau was not observed in a genetic or nutritional model of axonal degeneration or demyelination, suggesting that inflammation as detected in the brains of rats with EAE is the specific trigger of tau pathology. In summary, our data provide evidence that axonal damage in EAE and possibly MS is linked to tau pathology."],["dc.identifier.doi","10.1074/jbc.M409954200"],["dc.identifier.isi","000225960800106"],["dc.identifier.pmid","15494405"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/46980"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation.issn","0021-9258"],["dc.title","Hyperphosphorylation and aggregation of tau in experimental autoimmune encephalomyelitis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]