title: Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases.
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 Ca(2+) 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.
authors.affiliation: Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: Marie-Theres
authors.initials: MT
authors.lastname: Weil
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany; Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), 37075 Göttingen, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Möbius
authors.affiliation: Department of Neuropathology, University of Göttingen Medical Center, 37075 Göttingen, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Winkler
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany; Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), 37075 Göttingen, Germany.
authors.forename: Torben
authors.initials: T
authors.lastname: Ruhwedel
authors.affiliation: Department of Neuropathology, University of Göttingen Medical Center, 37075 Göttingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Wrzos
authors.affiliation: Institute of Clinical Neuroimmunology and Biomedical Center, Ludwig-Maximillians University, 80539 Munich, Germany.
authors.forename: Elisa
authors.initials: E
authors.lastname: Romanelli
authors.affiliation: Departments of Neurology, University of Denver, Denver, CO 80045, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Bennett
authors.affiliation: Neurobiology, Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
authors.forename: Lukas
authors.initials: L
authors.lastname: Enz
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Goebels
authors.affiliation: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany; Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), 37075 Göttingen, Germany.
authors.forename: Klaus-Armin
authors.initials: KA
authors.lastname: Nave
authors.affiliation: Institute of Clinical Neuroimmunology and Biomedical Center, Ludwig-Maximillians University, 80539 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kerschensteiner
authors.affiliation: Neurobiology, Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Schaeren-Wiemers
authors.affiliation: Department of Neuropathology, University of Göttingen Medical Center, 37075 Göttingen, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Stadelmann
authors.affiliation: Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany; Institute of Neuronal Cell Biology, Technical University Munich, 80805 Munich, Germany; German Center for Neurodegenerative Disease (DZNE), 6250 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany. Electronic address: msimons@gwdg.de.
authors.forename: Mikael
authors.initials: M
authors.lastname: Simons
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D004195:Disease Models, Animal; D004676:Myelin Basic Protein / Q000378:metabolism*; D009186:Myelin Sheath / Q000473:pathology*; D009471:Neuromyelitis Optica / Q000378:metabolism* / Q000473:pathology; D011917:Rats, Inbred Lew
chemical_list: C436006:Mbp protein, rat; D004676:Myelin Basic Protein