Most proteins undergo posttranslational modification such as acetylation, methylation, phosphorylation, biotinylation, and ubiquitination to regulate various cellular processes. Ubiquitin-targeted proteins from the ubiquitin-proteasome system (UPS) are degraded by 26S proteasome, along with this, deubiquitinating enzymes (DUBs) have specific activity against the UPS through detaching of ubiquitin on ubiquitin-targeted proteins. Balancing between protein expression and degradation through interplay between the UPS and DUBs is important to maintain cell homeostasis, and abnormal expression and elongation of proteins lead to diverse diseases such as cancer, diabetes, and autoimmune response. Therefore, development of DUB inhibitors as therapeutic targets has been challenging. In addition, understanding of the roles of DUBs in neurodegeneration, specifically brain diseases, has emerged gradually. This review highlights recent studies on the molecular mechanisms for DUBs, and discusses potential therapeutic targets for DUBs in cases of brain diseases.

大多数蛋白质经过翻译后修饰，例如乙酰化，甲基化，磷酸化，生物素化和泛素化，以调节各种细胞过程。来自泛素-蛋白酶体系统（UPS）的针对泛素的蛋白质被26S蛋白酶体降解，与此同时，去泛素化酶（DUB）通过泛素针对的蛋白质上泛素的分离而具有针对UPS的特异活性。通过UPS和DUB之间的相互作用，蛋白质表达与降解之间的平衡对于维持细胞稳态非常重要，蛋白质的异常表达和伸长会导致多种疾病，例如癌症，糖尿病和自身免疫反应。因此，开发DUB抑制剂作为治疗靶标具有挑战性。此外，了解DUB在神经变性中的作用，特别是脑部疾病，已经逐渐出现。这篇综述重点介绍了DUBs分子机制的最新研究，并讨论了在脑部疾病中DUBs的潜在治疗靶点。