Multiple sclerosis (MS) is the most common autoimmune disease of the CNS. The etiology of MS is still unclear but it is widely recognized that both genetic and environmental factors contribute to its pathogenesis. Immune signaling and responses are critically regulated by ubiquitination, a posttranslational modification that is promoted by ubiquitinating enzymes and inhibited by deubiquitinating enzymes (DUBs). Genome-wide association studies (GWASs) identified that polymorphisms in or in the vicinity of two human DUB genes TNFAIP3 and USP18 were associated with MS susceptibility. Studies with experimental autoimmune encephalomyelitis (EAE), an animal model of MS, have provided biological rationale for the correlation between these DUBs and MS. Additional studies have shown that other DUBs are also involved in EAE by controlling distinct cell populations. Therefore, DUBs are emerging as crucial regulators of MS/EAE and might become potential therapeutic targets for the clinical treatment of MS.

中文翻译：

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去泛素化酶（DUBs）：中枢神经系统自身免疫中双刃剑

多发性硬化症（MS）是中枢神经系统最常见的自身免疫性疾病。MS的病因尚不清楚，但已广泛认识到遗传和环境因素均对其发病机制有贡献。免疫信号转导和应答受到泛素化的严格调节，泛素化酶促进了翻译后修饰，而泛素化酶（DUBs）抑制了翻译后修饰。全基因组关联研究（GWAS）发现，两个人DUB基因TNFAIP3和USP18或附近的多态性与MS易感性相关。MS的动物模型实验性自身免疫性脑脊髓炎（EAE）的研究为这些DUB与MS之间的相关性提供了生物学原理。其他研究表明，其他DUB也通过控制不同的细胞群参与了EAE。因此，DUBs逐渐成为MS / EAE的关键调节剂，并可能成为MS临床治疗的潜在治疗靶标。