Raymond & Beverly Sackler School of Chemistry, Tel Aviv University , Tel Aviv 6997801, Israel.
Tel Aviv University Center for Nanoscience and Nanotechnology, Tel Aviv University , Tel Aviv 6997801, Israel.
J Am Chem Soc. 2016 Sep 21;138(37):12159-65. doi: 10.1021/jacs.6b04826. Epub 2016 Sep 6.
In demyelinating diseases such as multiple sclerosis, disrupted myelin structures impair the functional role of the sheath as an insulating layer for proper nerve conduction. Though the etiology and recovery pathways remain unclear, in vivo studies show alterations in the lipid and the adhesive protein (myelin basic protein, MBP) composition. We find that in vitro cytoplasmic myelin membranes with modified lipid composition and low MBP concentration, as in demyelinating disease, show structural instabilities and pathological phase transition from a lamellar to inverted hexagonal, which involve enhanced local curvature. Similar curvatures are also found in vivo in diseased myelin sheaths. In addition, MBP dimers form a correlated mesh-like network within the inner membrane space, only in the vicinity of native lipid composition. These findings delineate the distinct functional roles of dominant constituents in cytoplasmic myelin sheaths, and shed new light on mechanisms disrupting lipid-protein complexes in the diseased state.
在脱髓鞘疾病（如多发性硬化症）中，受损的髓鞘结构破坏了鞘作为适当神经传导绝缘层的功能作用。尽管病因和恢复途径仍不清楚，但体内研究表明脂质和黏附蛋白（髓鞘碱性蛋白，MBP）组成发生改变。我们发现，体外具有改变的脂质组成和低 MBP 浓度的细胞质髓鞘膜，如脱髓鞘疾病中的情况，表现出结构不稳定性和从层状到反向六方的病理相变，其中涉及增强的局部曲率。在患病的髓鞘鞘中也可以在体内发现类似的曲率。此外，只有在天然脂质组成附近，MBP 二聚体才会在内部膜空间内形成相关的网格状网络。这些发现描绘了细胞质髓鞘中主要成分的不同功能作用，并为在患病状态下破坏脂-蛋白复合物的机制提供了新的认识。
