Abstract：
White matter hyperintensities (WMHs) refer to a group of diseases with numerous etiologies while oligodendrocytes remain the centerpiece in the pathogenesis of WMHs. Ring Finger Protein 216 (RNF216) encodes a ubiquitin ligase, and its mutation begets WMHs, ataxia, and cognitive decline in patients. Yet no study has revealed the function of RNF216 in oligodendroglia and WHIs before. In this study, we summarized the phenotypes of RNF216-mutation cases and explored the normal distribution of RNF216 in distinct brain regions and neuronal cells by bioinformatic analysis. Furthermore, MO3.13, a human oligodendrocyte cell line, was applied to study the function alteration after RNF216 knockdown. As a result, WMHs were the most common symptom in RNF216-mutated diseases, and RNF216 was indeed relatively enriched in corpus callosum and oligodendroglia in humans. The downregulation of RNF216 in oligodendroglia remarkably hampered cell proliferation by inhibiting the Akt pathway while having no significant effect on cell injury and oligodendrocyte maturation. Combining clinical, bioinformatical, and experimental evidence, our study implied the pivotal role of RNF216 in WMHs which might serve as a potent target in the therapy of WMHs.
摘要：
白质高强度（WMHs）是指一组具有多种病因的疾病，而少突胶质细胞仍然是WMHs发病机理的核心。环指蛋白216（RNF216）编码泛素连接酶，它的突变会引起WMHs，共济失调,和患者的认知能力下降。然而，之前没有研究揭示RNF216在少突胶质细胞和WHIs中的功能。在这项研究中,我们总结了RNF216突变病例的表型,并通过生物信息学分析探讨了RNF216在不同脑区和神经元细胞中的正态分布.此外，MO3.13，人类少突胶质细胞细胞系，应用于研究RNF216敲低后的功能改变。因此,WMHs是RNF216突变疾病中最常见的症状，RNF216确实在人类的call体和少突胶质细胞中相对丰富。少突胶质细胞中RNF216的下调通过抑制Akt途径显著阻碍了细胞增殖,同时对细胞损伤和少突胶质细胞成熟没有显著影响。结合临床，生物信息学，和实验证据，我们的研究暗示了RNF216在WMHs中的关键作用,这可能是WMHs治疗的有效靶点.
