Chitkara College of Pharmacy, Chitkara University, Punjab, India.
Chitkara College of Pharmacy, Chitkara University, Punjab, India.
Life Sci. 2020 Nov 15;261:118459. doi: 10.1016/j.lfs.2020.118459. Epub 2020 Sep 19.
Rheumatoid arthritis is a chronic, inflammatory joint disease leading to inflammation of synovial membrane that lines the joints. This inflammation further progresses and results in destruction of joints and surrounding cartilages. The underlying factors can be oxidative stress, pro-inflammatory mediators, imbalance and attenuation between various enzymes and proteins (like nuclear factor erythroid 2 related factor 2/Nrf2 and ubiquitin). Protein degradation pathways comprises of lysosomal, proteasomal pathway, and autophagosome (that are carried out in mammalian cells) are regulated through ubiquitin. Ubiquitin proteasomal system is dominating pathway for carrying out non-lysosomal proteolysis of intracellularly proteins. Fundamental processes including cell cycle progression, process of division, apoptosis, modulation of immune responses and cell trafficking are regulated by process of ubiquitination. Ubiquitin proteasomal pathway (UPP) includes ubiquitin moieties which are covalently attached to proteins and guides them proteasome for degradation. Misfolded, oxidized and damaged proteins which are responsible for critical processes, are major targets of degradation process. Any alteration in this system leads to dysregulated cellular homeostasis; progressively leading to numerous diseases including rheumatoid arthritis. Factors including TAK1, TRAF6 undergo are required for the progression of disease and thus contributes towards pathology of inflammatory disorders such as rheumatoid arthritis. This review will include all linked aspects which contribute its major role in rheumatoid arthritis.
类风湿关节炎是一种慢性炎症性关节疾病，导致关节滑膜炎症。这种炎症进一步发展，导致关节和周围软骨的破坏。潜在因素可能是氧化应激、促炎介质、各种酶和蛋白质（如核因子红细胞 2 相关因子 2/Nrf2 和泛素）之间的失衡和衰减。蛋白质降解途径包括溶酶体、蛋白酶体途径和自噬体（在哺乳动物细胞中进行），通过泛素进行调节。泛素蛋白酶体系统是执行细胞内蛋白质非溶酶体水解的主要途径。包括细胞周期进展、分裂过程、细胞凋亡、免疫反应和细胞迁移的调节等基本过程都受到泛素化过程的调节。泛素蛋白酶体途径（UPP）包括共价连接到蛋白质上的泛素部分，并指导它们进入蛋白酶体进行降解。负责关键过程的错误折叠、氧化和受损蛋白质是降解过程的主要靶标。该系统的任何改变都会导致细胞内稳态失调，进而导致包括类风湿关节炎在内的许多疾病。包括 TAK1、TRAF6 在内的多种因素都需要参与疾病的进展，因此有助于炎症性疾病（如类风湿关节炎）的病理学发展。本综述将包括所有相关方面，以阐明其在类风湿关节炎中的主要作用。
