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Loss of myelin basic protein function triggers myelin breakdown in models of demyelinating diseases

Cell Reports. 2016 June 22. pii: S2211-1247(16)30727-6. DOI: 10.1016/j.celrep.2016.06.008. [Epub ahead of print]

Authors/Editors: Weil M-T, Möbius W, Winkler A, Ruhwedel T, Wrzos C, Romanelli E, Bennett J L, Enz L, Goebels N, Nave K-A, Kerschensteiner M, Schaeren-Wiemers N, Stadelmann C, Simons M
Publication Date: 2016

Graphic Abstract



•Characterization of myelin sheath pathology close its native state
•Vesiculation of inner sheath layers is a common feature of myelin pathology
•Loss of MBP function triggers myelin vesiculation
•Elevation of intracellular Ca2+ triggers MBP phase transition


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.


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