CAS Key Laboratory of Receptor Research, the National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
University of Chinese Academy of Sciences, Graduate School, No. 19A Yuquan Road, Beijing, 100049, China.
Glia. 2018 Jul;66(7):1302-1316. doi: 10.1002/glia.23306. Epub 2018 Feb 9.
Oligodendrocyte-formed myelin sheaths play important roles in the neuronal functions in the central nervous system. In demyelinating diseases, such as Multiple Sclerosis, the myelin sheaths are damaged and the remyelinating process is somehow hindered. Restoration of the myelin sheaths requires the differentiation of the oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs). To discover small molecule compounds that might promote the OPC to OL differentiation, a high-throughput screening system is established and L-ascorbyl-2-phosphate (As-2P), a stable form of Vitamin C (Vc), is found to greatly enhance the OPC to OL differentiation. As-2P promotes gradual expression of OL lineage markers, including O4, CNPase and MBP, in a dose- and time-dependent manner. It also facilitates the formation of myelin sheaths in OPC-neuron co-culture. As-2P also promotes the repair of the myelin sheaths in vivo and provides significant therapeutic effect in a cuprizone-mediated demyelination animal model. Interestingly, As-2P's function in promoting OPC differentiation is not related to its antioxidant activity. And an intracellular rather than an extracellular mechanism might be involved. Considering the safe use of Vc as a dietary supplement for many years, it might also be used as an alternative medicine for CNS demyelinating diseases.
少突胶质细胞形成的髓鞘在中枢神经系统的神经元功能中发挥着重要作用。在脱髓鞘疾病,如多发性硬化症中,髓鞘受损,髓鞘再生过程受到某种阻碍。髓鞘的修复需要少突胶质前体细胞(OPC)分化为成熟的少突胶质细胞(OL)。为了发现可能促进 OPC 向 OL 分化的小分子化合物,建立了高通量筛选系统,发现 L-抗坏血酸-2-磷酸(As-2P),一种稳定形式的维生素 C(Vc),可极大地促进 OPC 向 OL 分化。As-2P 以剂量和时间依赖的方式逐渐促进 OL 谱系标志物,包括 O4、CNPase 和 MBP 的表达。它还促进 OPC-神经元共培养中髓鞘的形成。As-2P 还促进体内髓鞘的修复,并在杯状朊病毒介导的脱髓鞘动物模型中提供显著的治疗效果。有趣的是,As-2P 促进 OPC 分化的功能与其抗氧化活性无关。并且可能涉及细胞内而不是细胞外机制。考虑到 Vc 作为膳食补充剂多年来的安全使用,它也可能被用作治疗 CNS 脱髓鞘疾病的替代药物。