Weil Marie-Theres, Möbius Wiebke, Winkler Anne, Ruhwedel Torben, Wrzos Claudia, Romanelli Elisa, Bennett Jeffrey L, Enz Lukas, Goebels Norbert, Nave Klaus-Armin, Kerschensteiner Martin, Schaeren-Wiemers Nicole, Stadelmann Christine, Simons Mikael
Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
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.
Cell Rep. 2016 Jul 12;16(2):314-322. doi: 10.1016/j.celrep.2016.06.008. Epub 2016 Jun 23.
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.
髓鞘分解是几种神经系统自身免疫性疾病的病理标志。我们利用自身抗体介导的脱髓鞘疾病动物模型，包括视神经脊髓炎（NMO）大鼠模型，来靶向髓鞘，发现髓鞘板层在髓鞘最内层区域分解为囊泡结构。我们证明，在这些模型中，在髓鞘膜层之间形成聚合物的髓鞘碱性蛋白（MBP）是靶点。细胞内Ca(2+)水平升高导致MBP网络解体和髓鞘囊泡化。我们提出，MBP分子从其凝聚态到可溶和非粘附态的异常相变是触发NMO以及可能其他脱髓鞘疾病中髓鞘分解的一种机制。
