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Cell Rep. 2016 Jul 12;16(2):314-322. doi: 10.1016/j.celrep.2016.06.008. Epub 2016 Jun 23.

Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases.

Author information

1
Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
2
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.
3
Department of Neuropathology, University of Göttingen Medical Center, 37075 Göttingen, Germany.
4
Institute of Clinical Neuroimmunology and Biomedical Center, Ludwig-Maximillians University, 80539 Munich, Germany.
5
Departments of Neurology, University of Denver, Denver, CO 80045, USA.
6
Neurobiology, Department of Biomedicine, University Hospital Basel, University of Basel, 4031 Basel, Switzerland.
7
Department of Neurology, Medical Faculty, Heinrich-Heine-University, 40225 Düsseldorf, Germany.
8
Institute of Clinical Neuroimmunology and Biomedical Center, Ludwig-Maximillians University, 80539 Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.
9
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.

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.

PMID:
27346352
PMCID:
PMC4949381
DOI:
10.1016/j.celrep.2016.06.008
[Indexed for MEDLINE]
Free PMC Article

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