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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

双氢青蒿素改善APP / PS1小鼠神经可塑性相关蛋白减少和神经元凋亡过多。

卷 17, 期 10, 2020

页: [916 - 925] 页: 10

弟呕挨: 10.2174/1567205017666201215124746

价格: $65

摘要

背景：阿尔茨海默氏病（AD）是全球范围内最严重的神经退行性疾病之一，其主要病理特征是细胞外老年斑（SP），随后的细胞内神经原纤维缠结（NFT）和最终神经元丢失和突触功能障碍。过度的细胞凋亡是不可逆神经元丢失的主要原因。因此，对于这些病理特征的治疗干预被认为是治疗或预防AD的有前途的策略。双氢青蒿素（DHA）是广泛用于疟疾的一线药物。我们之前的研究表明，DHA治疗可显着提高体内Aβ清除率，改善记忆力和认知缺陷，并在体内和体外恢复自噬通量。 方法：本研究旨在探讨DHA对APP / PS1双转基因小鼠神经元丢失的神经保护作用及其潜在机制。透射电子显微镜（TEM）分析表明，DHA显着降低了APP / PS1小鼠的内质网肿胀（ER）。蛋白质印迹分析表明，DHA上调了NeuN，NeuroD，MAP2和突触素的水平，并促进了神经突的长出。同时，DHA极大地纠正了脑源性神经营养因子（BDNF）的异常水平，并挽救了海马CA1区的神经元丢失。蛋白质印迹分析表明，DHA显着下调了全长caspase-3，裂解的caspase-3和Bax的蛋白质表达。同时，口服DHA治疗后抗凋亡蛋白Bcl-2的表达增加。 结果：总而言之，这些结果表明，DHA通过促进BDNF和其他神经可塑性相关蛋白的表达并抑制神经元凋亡的抑制作用来保护AD小鼠免受神经元丢失。

关键词: 阿尔茨海默氏病，β淀粉样蛋白，双氢青蒿素，细胞凋亡，突触素，BDNF。

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