SUMO修饰在神经系统疾病中的作用机制

The mechanism of SUMOylation in nervous system diseases

SUMO修饰作为一种新型动态可逆的翻译后修饰,因其在真核生物中具有重要的生物学功能而被广泛报道。该过程与泛素化修饰类似,通过对底物蛋白进行多步酶促反应以完成对靶蛋白的SUMO修饰和去SUMO修饰过程,进而影响底物蛋白的亚细胞定位、蛋白互作和稳定性等。SUMO修饰维持着机体稳态,因此,SUMO修饰过程失衡会引起正常生理过程的紊乱甚至失调,进而导致疾病的发生。近年来研究表明,SUMO修饰与神经系统疾病密切相关,SUMO修饰过程也参与了阿兹海默症、帕金森症、亨廷顿舞蹈症、肌萎缩性侧索硬化症、脑缺血、脊髓小脑共济失调以及癫痫猝死等疾病的发生与发展。随着对神经系统疾病研究的逐渐深入,尤其是SUMO修饰调控疾病关键蛋白分子机理的进一步解析,也同样为治疗神经性疾病提供了新的思路和潜在的药用靶点。本文主要总结了SUMO化修饰在神经系统疾病中的具体作用机制和研究进展,希望为后续的临床研究提供可行的治疗思路。

SUMOylation is a reversible post-translational modification process similar to ubiquitination. It has been found in many life processes by regulating the function, aggregation and stability of proteins by connecting to lysine residues of proteins. SUMOylation maintains the homeostasis of the body, so the imbalance of SUMOylation will cause the imbalance of normal physiological process, and then lead to the occurrence of diseases. Recent studies have found that SUMOylation also plays an important role in neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic Lateral Sclerosis, Cerebral ischemia, Spinocerebellar Ataxia and even sudden epilepsy. Now there has been a preliminary study on the mechanism and effect of SUMOylation, providing ideas and potential targets. This review mainly summarizes the specific mechanism and research progress of SUMOylation in neurological diseases, presuming to provide possible treatment strategies and pharmacological targets for follow-up clinical research.