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Abstract：
Remyelination is a regenerative process that restores the lost neurological function and partially depends on oligodendrocyte differentiation. Differentiation of oligodendrocytes spontaneously occurs after demyelination, depending on the cell intrinsic mechanisms. By combining a loss-of-function genomic screen with a web-resource-based candidate gene identification approach, we identified that dimethylarginine dimethylaminohydrolase 1 (DDAH1) is a novel regulator of oligodendrocyte differentiation. Silencing DDAH1 in oligodendrocytes prevented the expression of myelin basic protein in mouse oligodendrocyte culture with the change in expression of genes annotated with oligodendrocyte development. DDAH1 inhibition attenuated spontaneous remyelination in a cuprizone-induced demyelinated mouse model. Conversely, increased DDAH1 expression enhanced remyelination capacity in experimental autoimmune encephalomyelitis. These results provide a novel therapeutic option for demyelinating diseases by modulating DDAH1 activity.
摘要：
髓鞘再生是恢复失去的神经功能的再生过程,部分依赖于少突胶质细胞分化。少突胶质细胞的分化在脱髓鞘后自发发生，取决于细胞的内在机制。通过将功能丧失基因组筛选与基于网络资源的候选基因鉴定方法相结合，我们发现二甲基精氨酸二甲基氨基水解酶1（DDAH1）是少突胶质细胞分化的一种新型调节因子。在少突胶质细胞中沉默DDAH1会阻止小鼠少突胶质细胞培养物中髓鞘碱性蛋白的表达，并伴随着少突胶质细胞发育的基因表达发生变化。DDAH1抑制减弱了铜宗诱导的脱髓鞘小鼠模型中的自发髓鞘再生。相反，DDAH1表达增加可增强实验性自身免疫性脑脊髓炎的髓鞘再生能力.这些结果通过调节DDAH1活性为脱髓鞘疾病提供了新的治疗选择。
