α7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block a β-amyloid-induced neurotoxicity
α7 nicotinic receptor transduces signals to phosphatidylinositol 3-kinase to block a β-amyloid-induced neurotoxicity
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DOI：
10.1074/jbc.m008035200
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发表时间：
2001-04-27
影响因子：
4.8
通讯作者：
Akaike, A
中科院分区：
文献类型：
--
作者：
Kihara, T;Shimohama, S;Akaike, A
从分子和细胞到流行病学的多种证据表明，尼古丁传播与阿尔茨海默病（AD）的发病机制有关。在这里，我们展示了烟碱受体介导的抗β -淀粉样蛋白增强谷氨酸神经毒性的信号转导机制。尼古丁诱导的保护作用被α - 7尼古丁受体拮抗剂（α -bungarotoxin）、磷脂酰肌醇3-激酶（PI3K）抑制剂（LY294002和wortmannin）和Src抑制剂（PP2）抑制。磷酸化Akt （PI3K的一种效应物）和Bcl-2的水平在尼古丁作用下升高。α 7烟碱受体与PI3K p85亚基和Fyn有物理关联。这些发现表明，α - 7烟碱受体通过级联传递信号给PI3K，最终起到神经保护作用。这可能成为阿尔茨海默病新疗法的基础。
Multiple lines of evidence, from molecular and cellular to epidemiological, have implicated nicotinic transmission in the pathogenesis of Alzheimer's disease (AD). Here we show the signal transduction mechanism involved in nicotinic receptor-mediated protection against beta -amyloid-enhanced glutamate neurotoxicity. Nicotine-induced protection was suppressed by an alpha7 nicotinic receptor antagonist (alpha -bungarotoxin), a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002 and wortmannin), and a Src inhibitor (PP2). Levels of phosphorylated Akt, an effector of PI3K, and Bcl-2 were increased by nicotine. The alpha7 nicotinic receptor was physically associated with the PI3K p85 subunit and Fyn. These findings indicate that the alpha7 nicotinic receptor trans duces signals to PI3K in a cascade, which ultimately contributes to a neuroprotective effect. This might form the basis of a new treatment for AD.