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

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.