突触蛋白I片段促进α-突触核蛋白的聚集  

Synapsin I fragment promotes α-synuclein aggregation

作　　者：刘聪聪 孟兰霞 张振涛[1] Liu Congcong;Meng Lanxia;Zhang Zhentao(Department of Neurology,Renmin Hospital of Wuhan University,Wuhan 430060)

机构地区：[1]武汉大学人民医院神经内科,430060

出　　处：《卒中与神经疾病》2023年第1期3-8,共6页Stroke and Nervous Diseases

基　　金：国家重点研发计划(No.2019YFE0115900)。

摘　　要：目的 探讨突触蛋白I(Synapsin I,Syn I)被剪切后形成的C83片段对α-突触核蛋白聚集的影响。方法 在稳定表达α-突触核蛋白的HEK293细胞、小鼠原代神经元以及Tau P301S转基因小鼠体内分别过表达Syn I全长及其C83片段,通过细胞免疫荧光染色、蛋白免疫印迹技术以及免疫组织化学染色的方法观察Syn I全长及其C83片段对α-突触核蛋白磷酸化及聚集的影响。结果 Syn I C83片段促进HEK293细胞中α-突触核蛋白的磷酸化、泛素化以及聚集,并诱导小鼠原代神经元以及Tau P301S转基因小鼠体内α-突触核蛋白的磷酸化和聚集。结论 在细胞和动物模型中Syn I C83片段均可以促进α-突触核蛋白的聚集,这可能是Syn I C83片段导致认知功能障碍的重要原因之一。Objective To investigate the effect of synapsin I fragment(Syn I C83) on α-synuclein aggregation. Methods The synapsin I and Syn I C83 fragment were overexpressed in HEK293 cells stably expression α-synuclein, primary mouse neurons, and Tau P301S transgenic mice. The effects of synapsin I and Syn I C83 fragment on α-synuclein phosphorylation and aggregation were observed by immunofluorescence staining, Western blot, and immunohistochemical staining. Results Syn I C83 fragment promotes α-synuclein phosphorylation, ubiquitination, and aggregation in HEK293 cells. Syn I C83 fragment also induces α-synuclein phosphorylation and aggregation in primary neurons and Tau P301S transgenic mice. Conclusion Syn I C83 fragment promoted the aggregation of α-synuclein in cellular and animal models. This may contribute to cognitive impairment mediated by Syn I C83 fragment.

关 键 词：突触蛋白I 天冬酰胺内肽酶 Α-突触核蛋白 阿尔茨海默病 

分 类 号：R742[医药卫生—神经病学与精神病学]