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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

星形细胞α7烟碱受体激活通过PI3K/Akt信号通路上调内源性αb-晶体蛋白抑制淀粉样蛋白β聚集

卷 16, 期 1, 2019

页: [39 - 48] 页: 10

弟呕挨: 10.2174/1567205015666181022093359

价格: $65

摘要

背景: β-淀粉样蛋白（Aβ）聚集在阿茨海默症（AD）发病机制中起着重要作用，星形胶质细胞能显著抑制Aβ聚集。在AD脑中检测到的星形细胞α7神经烟碱乙酰胆碱受体（nAChR）上调与Aβ沉积密切相关。然而，星形细胞α7 nAChRs与Aβ聚集之间的关系尚不明确。 方法: 用尼古丁或磷脂酰肌醇3-激酶（PI3K）-蛋白激酶B（AKT）抑制剂联合治疗后，测定星形细胞溶解液和培养基中的aβ低聚物水平。采用Western blotting法测定了不同时间尼古丁或α7 nAChR拮抗剂联合作用以及与PI3K或丝裂原活化蛋白激酶激酶1/2（MEK1/2）抑制剂共孵育的星形胶质细胞中αb-晶体蛋白（cryab）的水平。 结果: 本研究中，初级星形胶质细胞中的尼古丁预处理显著抑制aβ聚集并上调内源性星形胶质细胞Cryab，而选择性α7-nachr拮抗剂预处理可逆转尼古丁介导的神经保护作用。此外，PI3K抑制剂LY294002抑制了这种对Aβ聚集的神经保护作用。尼古丁预处理显著增加星形胶质细胞中PI3K效应物磷酸化Akt的水平。 结论: α7 nAChR激活和PI3K/Akt信号转导通过调节内源性星形细胞Cryab促进烟碱介导的抗aβ聚集的神经保护。

关键词: 阿茨海默症，β-淀粉样蛋白聚集，α7神经烟碱乙酰胆碱受体，PI3K/Akt信号通路，αB晶体蛋白，痴呆

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