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Dissecting the signaling pathway of nicotine‐mediated neuroprotection in a mouse Alzheimer disease model
Author(s) -
Liu Qiang,
Zhang Jie,
Zhu Hua,
Qin Chuan,
Chen Qi,
Zhao Baolu
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-5841com
Subject(s) - nicotine , neuroprotection , mapk/erk pathway , kinase , pharmacology , signal transduction , chemistry , rna interference , neuroscience , microbiology and biotechnology , biology , biochemistry , rna , gene
Nicotine has a therapeutic benefit in treating Alzheimer's disease (AD). In the present study we show that nicotine decreases accumulation of β‐amyloid (Aβ) in the cortex and hippocampus of APP (V717I) transgenic mice. Nicotine prevents activation of NF‐κB 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 α7 nAChR. Nicotine decreases Aβ via the activation of a7nAChRs through MAPK, NF‐κB, 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, Q., Zhang, J., Zhu, H., Qin, C., Chen, Q., Zhao, B. Dissecting the signaling pathway of nicotine‐mediated neuroprotection in a mouse Alzheimer disease model. FASEB J. 21, 61–73 (2007)