Dissecting the signaling pathway of nicotine-mediated neuroprotection in a mouse Alzheimer disease model

被引:105
作者
Liu, Qiang
Zhang, Jie
Zhu, Hua
Qin, Chuan
Chen, Qi
Zhao, Baolu
机构
[1] Acad Sinica, Inst Biophys, State Key Lab Brain & Cognit Sci, Beijing 100101, Peoples R China
[2] Chinese Acad Sci, Grad Sch, Beijing, Peoples R China
[3] Chinese Acad Sci, Inst Lab Anim Sci, Beijing, Peoples R China
[4] Salk Inst Biol Studies, La Jolla, CA 92037 USA
[5] Shanghai Univ Tradit Chinese Med, E Inst NO & Inflammat, Shanghai, Peoples R China
关键词
AD; alpha; 7nAChRs; signal pathway;
D O I
10.1096/fj.06-5841com
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:61 / 73
页数:13
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