Dissecting the signaling pathway of nicotine-mediated neuroprotection in a mouse Alzheimer disease model
Dissecting the signaling pathway of nicotine-mediated neuroprotection in a mouse Alzheimer disease model
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DOI：
10.1096/fj.06-5841com
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发表时间：
2007-01-01
期刊：
影响因子：
4.8
通讯作者：
Zhao, Baolu
中科院分区：
文献类型：
--
作者：
Liu, Qiang;Zhang, Jie;Zhao, Baolu
尼古丁在治疗阿尔茨海默病（AD）方面具有治疗益处。在本研究中，我们表明尼古丁减少APP（V717 I）转基因小鼠皮质和海马中β-淀粉样蛋白（A β）的积累。尼古丁通过抑制MAP激酶（MAPK）的活化来防止NF-κ B和c-Myc的活化。结果，诱导型NOS的活性和NO的产生被下调。RNA干扰实验表明，上述尼古丁介导的过程需要α 7 nAChR。尼古丁通过MAPK、NF-κ B和c-myc途径激活α 7 nAChR降低A β。尼古丁还抑制该小鼠系中的细胞凋亡和细胞周期进程。本研究对尼古丁介导的神经保护信号通路的剖析为开发治疗AD的药物靶点提供了机制基础。
Nicotine has a therapeutic benefit in treating Alzheimer's disease ( AD). In the present study we show that nicotine decreases accumulation of beta-amyloid ( A beta) in the cortex and hippocampus of APP ( V717I) transgenic mice. Nicotine prevents activation of NF-kappa B and c-Myc by inhibiting the activation of MAP kinases ( MAPKs). As a result, the activity of inducible NOS and the production of NO are down-regulated. RNA interference experiments show that the above nicotine-mediated process requires alpha 7 nAChR. Nicotine decreases A beta via the activation of alpha 7nAChRs through MAPK, NF-kappa B, and c-myc pathways. Nicotine also inhibits apoptosis and cell cycle progression in this mouse line. The dissected signaling pathway of nicotine-mediated neuroprotection in the present study provides a mechanistic basis for the potential development of drug targets for treating AD.