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 (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.
Liu
Qiang
Q
State Key laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Academia Sinica, Beijing, China.
Zhang
Jie
J
Zhu
Hua
H
Qin
Chuan
C
Chen
Qi
Q
Zhao
Baolu
B
D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D004789:Enzyme Activation; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D034622:RNA Interference; D011978:Receptors, Nicotinic / Q000378:metabolism; D015398:Signal Transduction; D064569:alpha7 Nicotinic Acetylcholine Receptor
D016564:Amyloid beta-Protein Precursor; C579166:Chrna7 protein, mouse; D017931:DNA Primers; D016328:NF-kappa B; D018696:Neuroprotective Agents; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009569:Nitric Oxide; D009538:Nicotine; D052247:Nitric Oxide Synthase Type II; D020928:Mitogen-Activated Protein Kinases