Department of Medical Biotechnology, Yeungnam University, Gyeongsan 38541, Korea.
Research Institute of Cell Culture, Yeungnam University, Gyeongsan 38541, Korea.
Cells. 2022 Mar 24;11(7):1093. doi: 10.3390/cells11071093.
Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease associated with the central nervous system (CNS). Autoimmunity is caused by an abnormal immune response to self-antigens, which results in chronic inflammation and tissue death. Ubiquitination is a post-translational modification in which ubiquitin molecules are attached to proteins by ubiquitinating enzymes, and then the modified proteins are degraded by the proteasome system. In addition to regulating proteasomal degradation of proteins, ubiquitination also regulates other cellular functions that are independent of proteasomal degradation. It plays a vital role in intracellular protein turnover and immune signaling and responses. The ubiquitin-proteasome system (UPS) is primarily responsible for the nonlysosomal proteolysis of intracellular proteins. The 26S proteasome is a multicatalytic adenosine-triphosphate-dependent protease that recognizes ubiquitin covalently attached to particular proteins and targets them for degradation. Damaged, oxidized, or misfolded proteins, as well as regulatory proteins that govern many essential cellular functions, are removed by this degradation pathway. When this system is affected, cellular homeostasis is altered, resulting in the induction of a range of diseases. This review discusses the biochemistry and molecular biology of the UPS, including its role in the development of MS and proteinopathies. Potential therapies and targets involving the UPS are also addressed.
多发性硬化症（MS）是一种与中枢神经系统（CNS）相关的自身免疫性、神经退行性疾病。自身免疫是由针对自身抗原的异常免疫反应引起的，导致慢性炎症和组织死亡。泛素化是一种翻译后修饰，其中泛素分子通过泛素化酶附着到蛋白质上，然后修饰的蛋白质被蛋白酶体系统降解。除了调节蛋白酶体对蛋白质的降解外，泛素化还调节其他与蛋白酶体降解无关的细胞功能。它在细胞内蛋白质周转和免疫信号转导和反应中起着至关重要的作用。泛素-蛋白酶体系统（UPS）主要负责细胞内蛋白质的非溶酶体降解。26S 蛋白酶体是一种多催化的三磷酸腺苷依赖性蛋白酶，它识别与特定蛋白质共价连接的泛素，并将其作为降解的靶标。通过这种降解途径，可以去除受损、氧化或错误折叠的蛋白质以及调节许多基本细胞功能的调节蛋白。当这个系统受到影响时，细胞的内稳态就会发生改变，导致一系列疾病的发生。本文综述了 UPS 的生物化学和分子生物学，包括其在 MS 和蛋白病发展中的作用。还讨论了涉及 UPS 的潜在治疗方法和靶点。
