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

2006; Wiley; Volume: 21; Issue: 1 Linguagem: Inglês

10.1096/fj.06-5841com

1530-6860

Qiang Liu, Jie Zhang, Hua Zhu, Chuan Qin, Qi Chen, Baolu Zhao,

Computational Drug Discovery Methods

Nicotine has a therapeutic benefit in treating Alzheimer's disease (AD). In the present study we show that nicotine decreases accumulation of beta-amyloid (Abeta) in the cortex and hippocampus of APP (V717I) transgenic mice. Nicotine prevents activation of NF-kappaB 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 alpha7 nAChR. Nicotine decreases Abeta via the activation of alpha7nAChRs through MAPK, NF-kappaB, 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.