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Research Article

主动免疫疗法与12聚体Aβ1-42组装疫苗在3×Tg-AD老年小鼠中显示功效

卷 21, 期 1, 2021

发表于: 27 April, 2020

页: [45 - 55] 页: 11

弟呕挨: 10.2174/1566524020666200427101231

价格: $65

摘要

背景：阿尔茨海默氏病（AD）是最常见的进行性神经退行性疾病，其特征是老年斑和神经原纤维缠结（NFT）。淀粉样蛋白低聚物假说表明体内毒性低聚物的积累可能会损害记忆和突触功能。 方法：在本研究中，开发了一种新型的重组嵌合12×（Aβ1-15-Th）抗原作为12聚体Aβ1-42组装疫苗。我们设计了这种12×（Aβ1-15-Th）抗原，以使用十二倍的Aβ1-15（人类Aβ1-42的B细胞表位）和外来人类T辅助（Th）表位（作为T）模拟Aβ1-42的组装状态。 Aβ1-42）构建体的细胞表位。在C57 / BL6小鼠上测试了其作为亚单位疫苗的免疫原性，并通过将其应用于AD小鼠显示了其功效。 结果：这种12x（Aβ1-15-Th）疫苗在3xTg-AD和C57 / BL6小鼠中诱导了强大的Aβ特异性抗体。作为AD的早期免疫治疗剂，12×（Aβ1-15-Th）疫苗显着改善了3×Tg-AD衰老小鼠的行为表现，并降低了大脑中可溶性Aβ低聚物和可溶性Aβ的水平。在3只Tg-AD老龄小鼠中，用12x（Aβ1-15-Th）疫苗免疫治疗可以预防Aβ诱导的突触蛋白减少，这表明它对大脑具有神经保护作用。 结论：针对Aβ寡聚体病理构象的新型重组12×（Aβ1-15-Th）嵌合疫苗在临床前AD模型小鼠中显示出明显的神经保护作用，表明它是预防AD的良好候选疫苗。

关键词: 阿尔茨海默氏病，淀粉样β蛋白，嵌合疫苗，免疫疗法，钙蛋白酶，突触蛋白。

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