高尔基体破碎对tau蛋白过度磷酸化的影响

发布时间：2018-05-24 21:45

本文选题：阿尔茨海默病 + 高尔基体破碎　；参考：《华中科技大学》2013年硕士论文

【摘要】：背景：阿尔茨海默病（Alzheimer’s Disease,AD）是一种进行性的神经退行性疾病，其特征性的病理改变是细胞内的神经原纤维缠结（NFTs），其主要成分是微管相关蛋白tau的过度磷酸化。鉴于tau蛋白过度磷酸化是AD神经元发生退行性变性的重要标志，研究tau蛋白过度磷酸化的上游因素对阐明AD神经元损伤机制、寻找有效防治靶点具有重要意义。方法：4,8,13和16月龄的C57BL/6雄性小鼠和6个月APP/PS1转基因小鼠（每个年龄组4-5只）进行神经元的超微结构研究。通过Western Blot方法检测4,8,13和16月龄的C57BL/6雄性小鼠（每个年龄组4-5只）的高尔基基质蛋白和tau蛋白在脑中的表达。所有的C57BL/6小鼠由华中科技大学同济医学院动物实验中心提供。动物于宽松适宜的环境中饲养，自由饮水，室温保持在恒定的温(26±2°C)。本实验过程中，所有的动物实验均严格遵守神经科学协会颁布的《动物使用政策》。AD模型鼠APP/PS1转基因敲除小鼠脑组织样本来自于北京大学张岩教授赠予。运用细胞免疫荧光研究高尔基破碎时高尔基基质蛋白与tau的过度磷酸化间的关系。结果：C57BL/6小鼠大脑神经元内高尔基体破碎和tau蛋白磷酸化水平随年龄增长不断增加。布雷菲德菌素A和诺考达唑通过HEK293/tau细胞内的高尔基体破碎介导tau蛋白过度磷酸化。结论：在AD小鼠中，，神经元内高尔基体破碎随年龄增加不断增多，且高尔基体破碎是tau蛋白过度磷酸化的上游因素之一。
[Abstract]:Background: Alzheimer's disease (Alzheimer's disease) is a progressive neurodegenerative disease. Its characteristic pathological change is intracellular neurofibrillary tangles (NFTs), the main component of which is the hyperphosphorylation of microtubule-associated protein (tau). Since excessive phosphorylation of tau protein is an important marker for the degeneration of AD neurons, it is important to study the upstream factors of tau hyperphosphorylation in order to elucidate the mechanism of AD neuron injury and to find effective targets for prevention and treatment. Methods the ultrastructure of neurons in C57BL/6 male mice aged 13 and 16 months and APP/PS1 transgenic mice at 6 months old (4-5 mice per age group) were studied. The expression of Golgi matrix protein and tau protein in the brain of C57BL/6 male mice aged 13 and 16 months (4-5 mice in each age group) was detected by Western Blot method. All C57BL/6 mice were provided by the Animal Laboratory Center of Tongji Medical College, Huazhong University of Science and Technology. The animals were kept in a relaxed and suitable environment, drinking water freely and keeping a constant temperature of 26 卤2 掳C ~ (-1) at room temperature. In the course of this experiment, all animal experiments strictly comply with the animal use policy promulgated by the Neuroscience Association. The brain tissue samples of APP/PS1 transgenic knockout mice of AD model mice were donated by Professor Zhang Yan of Peking University. The relationship between Golgi matrix protein and excessive phosphorylation of tau was studied by cell immunofluorescence. Results the levels of Golgi body fragmentation and tau protein phosphorylation in brain neurons of C57BL / 6 mice increased with age. Blefedzein A and nocodazole mediated excessive phosphorylation of tau protein through Golgi body fragmentation in HEK293/tau cells. Conclusion: in AD mice, the fragmentation of Golgi body in neurons increases with age, and Golgi body fragmentation is one of the upstream factors of excessive phosphorylation of tau protein.
【学位授予单位】：华中科技大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R749.16

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