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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

纳米粒子包裹的Bryostatin-1在体外激活αα-分泌酶和PKC异构体，并促进阿尔茨海默氏病小鼠模型中空间学习的获取和保留

卷 17, 期 14, 2020

页: [1302 - 1310] 页: 9

弟呕挨: 10.2174/1567205018666210218155835

价格: $65

摘要

背景：阿尔茨海默氏病（AD）动物模型已揭示了Bryostatin-1的神经保护作用，该作用是由新型PKC亚型的激活，β-淀粉样蛋白的抑制以及炎症和血管生成事件的下调介导的，这使得Bryostatin-1成为降低与AD相关的有吸引力的候选药物神经，血管和认知障碍。 目的：为了进一步增强Bryostatin-1的功效，制备了纳米颗粒包裹的Bryostatin-1制剂。 方法：我们在神经元PKC-d，PKC-e亚型，α-分泌酶的体外模型中比较了纳米封装的Bryostatin-1和未经修饰的Bryostatin-1，并在空间记忆AD小鼠模型（BC3-Tg （APPswe，PSEN1 dE9）85Dbo / J小鼠）。 结果：我们发现，在PKC-δ和-ε和α-分泌酶激活试验中，纳米胶囊化的Bryostatin-1制剂显示的活性大于或等于未修饰的Bryostatin-1的活性。接下来，我们评估了纳米胶囊化Bryostatin-1制剂的处理如何促进莫里斯水迷宫中的空间学习。在测试前一周将AD转基因小鼠（6.5至8个月大）用纳米颗粒包封的Bryostatin-1制剂（1、2.5或5μg/小鼠）治疗，每周三次，然后每天进行5天的测试。在整个采集阶段，用纳米囊包埋的Bryostatin-1处理的小鼠具有较短的潜伏期，在靶区域的％时间增加和在相反象限的％时间减少。两周后未进行药物治疗，对小鼠进行了保留测试。纳米胶囊化的Bryostatin-1处理过的小鼠发现逃逸平台的潜伏期较短，表明保留了空间记忆。 结论：这些数据表明，使用强效纳米粒子包裹的Bryostatin-1制剂可以治疗与AD相关的认知缺陷。

关键词: 阿尔茨海默氏症，痴呆，分泌酶，PKC，神经退行性疾病，大脑皮层。

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