蛋白质拟素化修饰在炎症性疾病中的作用

doi:10.3969/j.issn.1006-7795.2026.02.008

摘要/Abstract

摘要： 蛋白质拟素化修饰是一种将神经前体细胞表达发育调控蛋白8（neural precursor cell expressed developmentally downregulated protein 8, NEDD8）共价修饰至靶蛋白的重要翻译后修饰过程，已被证实对细胞增殖、凋亡及信号转导等关键生物学事件具有调控作用。近年研究显示，蛋白质拟素化修饰与炎症性疾病的发生发展密切相关。本文首先系统综述了拟素化级联反应的生物化学过程及其调控机制，进而深入探讨其通过调控炎症信号通路关键蛋白发挥作用的过程，揭示该修饰对中性粒细胞、巨噬细胞、树突状细胞等天然免疫细胞及适应性免疫细胞特征与功能的核心调控作用。随后重点评述了蛋白质拟素化修饰在炎症性肠病、类风湿性关节炎、肝纤维化、胰腺炎、动脉粥样硬化及急性肺损伤等炎症性疾病中的具体作用机制，并探讨其作为治疗靶点的潜力。最后，针对当前小分子拟素化抑制剂（特别是MLN4924与TAS4464）在炎症治疗中的应用前景，阐述了其潜在临床价值，并提出未来研究需解决的关键问题与发展方向。

关键词: 拟素化, 神经前体细胞表达发育调控蛋白8, MLN4924, 免疫细胞, 炎症通路, 去拟素化

Abstract: The neddylation of proteins, which involves tagging substrate proteins with neural precursor cell-expressed developmentally down-regulated protein 8 (NEDD8), is one of the most important post-translational modifications. It has been shown to play significant roles in various biological processes such as cell growth, apoptosis, and signal transduction. Recent research has found a close association between protein neddylation and the occurrence and development of inflammatory diseases. This article begins by reviewing the neddylation cascade, including its biochemical processes and regulation, and further expounds on its effects by regulating key proteins in inflammatory signaling pathways, discovering that it acts as a crucial regulator for the characteristics and functions of innate immune cells (neutrophils, macrophages, and dendritic cells) as well as adaptive immune cells. Subsequently, we focus on reviewing the roles and mechanisms of protein neddylation in various inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, liver fibrosis, pancreatitis, atherosclerosis, and acute lung injury. The potential of protein neddylation as a therapeutic target is discussed. Finally, we discussed the significance and potential clinical values of current small-molecule neddylation inhibitors (particularly MLN4924 and TAS4464) as an promising therapeutic approach in the treatment of inflammation, further, we proposed possible future research directions and key issues to be addressed.

Key words: neddylation, neural precursor cell expressed developmentally downregulated protein 8, MLN4924, immune cells, inflammatory signaling pathway, deneddylation

中图分类号:

Q291

刘真真, 谢萍. 蛋白质拟素化修饰在炎症性疾病中的作用[J]. 首都医科大学学报, 2026, 47(2): 275-284.

Liu Zhenzhen, Xie Ping. Protein neddylation and its role in inflammatory diseases[J]. Journal of Capital Medical University, 2026, 47(2): 275-284.

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