Data from: Myelin basic protein induces neuron-specific toxicity by directly damaging the neuronal plasma membrane

The central nervous system (CNS) insults may cause massive demyelination and lead to the release of myelin-associated proteins including its major component myelin basic protein (MBP). MBP is reported to induce glial activation but its effect on neurons is still little known. Here we found that MBP specifically bound to the extracellular surface of the neuronal plasma membrane and induced neurotoxicity in vitro. This effect of MBP on neurons was basicity-dependent because the binding was blocked by acidic lipids and competed by other basic proteins. Further studies revealed that MBP induced damage to neuronal membrane integrity and function by depolarizing the resting membrane potential, increasing the permeability to cations and other molecules, and decreasing the membrane fluidity. At last, artificial liposome vesicle assay showed that MBP directly disturbed acidic lipid bilayer and resulted in increased membrane permeability. These results revealed that MBP induces neurotoxicity through its direct interaction with acidic components on the extracellular surface of neuronal membrane, which may suggest a possible contribution of MBP to the pathogenesis in the CNS disorders with myelin damage.

中枢神经系统（central nervous system，CNS）损伤可引发大规模髓鞘脱失，并诱导髓鞘相关蛋白释放，其主要组分为髓鞘碱性蛋白（myelin basic protein，MBP）。已有研究表明，髓鞘碱性蛋白可诱导神经胶质激活，但其对神经元的作用仍鲜为人知。本研究发现，髓鞘碱性蛋白可特异性结合神经元质膜的细胞外表面，并在体外诱导神经毒性。髓鞘碱性蛋白对神经元的该作用具有碱性依赖性：其结合过程可被酸性脂质阻断，且可被其他碱性蛋白竞争性抑制。进一步研究显示，髓鞘碱性蛋白可通过使静息膜电位去极化、提升阳离子及其他分子的膜通透性、降低膜流动性，破坏神经元膜的完整性与功能。最后，人工脂质体囊泡实验表明，髓鞘碱性蛋白可直接干扰酸性脂质双层，导致膜通透性升高。上述研究结果揭示，髓鞘碱性蛋白可通过与神经元细胞膜外表面的酸性成分直接相互作用诱导神经毒性，这或提示髓鞘碱性蛋白可能在髓鞘损伤相关中枢神经系统疾病的发病机制中发挥潜在作用。