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当代阿耳茨海默病研究

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ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

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Research Article

白藜芦醇挽救了Tau病小鼠模型中Tau诱导的认知缺陷和神经病理学

卷 16, 期 8, 2019

页: [710 - 722] 页: 13

弟呕挨: 10.2174/1567205016666190801153751

价格: $65

摘要

背景：阿尔茨海默氏病（AD）的特征是存在由微管相关蛋白tau组装的细胞外淀粉样β（Aβ）斑块和神经内神经原纤维缠结。越来越多的证据表明，tau病理学在AD进展中起重要作用。先前已证明白藜芦醇（RSV）可通过抑制Aβ生成和Aβ诱导的神经细胞毒性来发挥抗AD的神经保护作用，但其对tau病理学的作用尚不清楚。 方法：通过硫黄素T荧光和透射电镜观察RSV对tau聚集的影响。通过MTT测定评估RSV对tau寡聚物诱导的细胞毒性的作用，并通过免疫细胞化学确定N2a细胞对胞外tau的吸收。对6个月大的PS19雄性小鼠每天一次口服RSV或赋形剂治疗5周。使用莫里斯水迷宫测试，对象识别测试和Y迷宫测试确定认知能力。通过免疫印迹，免疫染色和ELISA分别评估了小鼠脑中的磷酸化tau蛋白，胶质增生，促炎细胞因子如TNF-α和IL-1β以及包括突触素和PSD95在内的突触蛋白的水平。 结果：RSV显着抑制tau聚集和tau寡聚物诱导的细胞毒性，并阻止N2a细胞摄取胞外tau寡聚物。当应用于PS19小鼠时，RSV治疗可有效挽救认知缺陷，减少小鼠大脑中磷酸化tau，神经发炎和突触丧失的水平。 结论：这些发现表明RSV对于AD和其他疾病具有潜在的治疗潜力。

关键词: 白藜芦醇，阿尔茨海默氏病，tau，低聚物，神经炎症，突触丧失。

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