Alzheimer's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Alzheimer's Disease, including details on diagnosis, memory loss, heredity, treatment, medication.

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

Liu Q, Zhang J, Zhu H, Qin C, Chen Q, Zhao B

State Key laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Academia Sinica, Beijing, China.

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.

Published 29 December 2006 in FASEB J, 21(1): 61-73.
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