α-突触核蛋白的异常修饰及在帕金森病中的作用机制  

Abnormal modification of alpha-synuclein and its mechanism in Parkinson’s disease

作　　者：齐雪 李家慧 朱远峰 禹璐 王鹏[1,2] Qi Xue;Li Jiahui;Zhu Yuanfeng;Yu Lu;Wang Peng(Department of Human Anatomy,School of Basic Medical Sciences,Beihua University,Jilin 132013,Jilin Province,China;Laboratory of Neurodegenerative Diseases,School of Basic Medical Sciences,Beihua University,Jilin 132013,Jilin Province,China)

机构地区：[1]北华大学基础医学院人体解剖学教研室,吉林省吉林市132013 [2]北华大学基础医学院神经退行性疾病研究室,吉林省吉林市132013

出　　处：《中国组织工程研究》2024年第8期1301-1306,共6页Chinese Journal of Tissue Engineering Research

基　　金：吉林省自然科学基金(YDZJ202201ZYTS575),项目负责人:王鹏;吉林省卫生与健康技术创新项目(2018J083),项目负责人:王鹏;北华大学研究生创新项目(2021017),项目负责人:齐雪。

摘　　要：背景:因α-突触核蛋白异常聚集而形成的路易体是帕金森病特征性病理变化。近年多项研究揭示α-突触核蛋白聚集体的形成与其翻译后修饰关系密切。α-突触核蛋白的磷酸化、硝基化、乙酰化、泛素化等修饰在帕金森病的发病和进展中的作用得到广泛关注。目的:通过文献综述的方法阐述关于α-突触核蛋白修饰类型、修饰位点对帕金森病的特征性病理形成和进展的影响。方法:由第一作者系统检索中国知网和PubMed数据库,以“α-突触核蛋白,帕金森病,磷酸化,乙酰化,泛素化,硝基化”为中文检索词,以“α-Synuclein,Parkinson’s disease,phosphorylation,acetylation,ubiquitination,nitration”为英文检索词,收集整理近年来与α-突触核蛋白异常修饰相关的文献,最终纳入61篇文献进行综述分析。结果与结论:①α-突触核蛋白异常修饰与其蛋白结构和其带有正负电荷密切相关,其氨基端带有正电荷,易发生泛素化和乙酰化修饰;其中心疏水区域因其疏水特性易形成β片层结构,其羧基端带有负电荷,是主要磷酸化修饰区域。②磷酸化修饰位点可促进磷酸化修饰并与α-突触核蛋白的聚集密切相关,而蛋白激酶可靶向激活翻译修饰,可能有助于促进或抑制聚集体形成。③α-突触核蛋白的降解途径主要发挥清除病理性蛋白的作用,各种激酶催化促使蛋白泛素化修饰后,使其功能受损,导致蛋白异常堆积,从而加重神经退变。④α-突触核蛋白的氨基端经过乙酰化修饰后,可提升蛋白对细胞膜的穿梭能力,减缓蛋白聚集,可能为神经细胞保护靶点,但是在突变型蛋白发生乙酰化修饰后反而产生相反作用。⑤α-突触核蛋白的硝基化修饰主要与氧化应激相关,在活性氧的作用下,硝基化修饰的蛋白聚集倾向增强。⑥由于α-突触核蛋白不同翻译后修饰产生的影响各异,因此阐明其翻译后修饰的主要机制,抑制�BACKGROUND:The formation of Lewy bodies due to abnormalα-synuclein aggregation is a characteristic pathological change in Parkinson’s disease.In recent years,several studies have revealed that the formation ofα-synuclein aggregates is closely related to its post-translational modifications.The modification ofα-synuclein such as phosphorylation,nitration,acetylation,and ubiquitination has attracted extensive attention in the pathogenesis and progression of Parkinson’s disease.OBJECTIVE:To review the research progress in the effect of modification types and sites ofα-synuclein on the characteristic pathological formation and progression of Parkinson’s disease.METHODS:PubMed and CNKI databases were searched by the first author with the key words of“α-synuclein,Parkinson’s disease,phosphorylation,acetylation,ubiquitination,nitration”in English and Chinese respectively to collect and sort out the literature related to abnormal modification ofα-synuclein in recent years.Finally,61 articles were included for further review.RESULTS AND CONCLUSION:Abnormal modification ofα-synuclein is closely related to its protein structure and its positive and negative charges.Its amino terminus is positively charged and prone to ubiquitination and acetylation modifications.The central hydrophobic region is prone to formingβ-pleated sheet due to its hydrophobic property.The carboxyl terminus is negatively charged,which is the main phosphorylation modification region.Phosphorylation modification sites promote phosphorylation modification and are closely related toα-synuclein aggregation,while protein kinases can target the activation of translational modifications,which may help to promote or inhibit aggregate formation.The degradation pathway ofα-synuclein mainly plays a role in removing pathological proteins.Various kinase catalysts contribute to impaired protein ubiquitination modifications that lead to abnormal protein accumulation,thereby exacerbating neurodegeneration.The amino-terminal acetylation ofα-synuc

关 键 词：Α-突触核蛋白 帕金森病 聚集体 磷酸化 酪氨酸 乙酰化 泛素化 硝基化 发病机制 基因突变 

分 类 号：R452[医药卫生—治疗学] R363[医药卫生—临床医学] R74