Nicotine attenuates β-amyloid-induced neurotoxicity by regulating metal homeostasis

• Published in: The FASEB journal Vol. 20; no. 8; pp. 1212 - 1214
• Main Authors: Zhang, Jie, Liu, Qiang, Chen, Qi, Liu, Nian-Qing, Li, Fu-Liang, Lu, Zhong-Bing, Qin, Chuan, Zhu, Hua, Huang, Yu-Ying, He, Wei, Zhao, Bao-Lu
• Format: Journal Article
• Language: English
• Published: United States The Federation of American Societies for Experimental Biology 01.06.2006
• Subjects: Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Amyloidosis - metabolism; Amyloidosis - pathology; Animals; Cell Survival - drug effects; Copper - antagonists & inhibitors; Copper - metabolism; Copper - pharmacology; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Homeostasis; Humans; Metals - metabolism; Mice; Mice, Transgenic; Molecular Chaperones - metabolism; Neuroprotective Agents - pharmacology; Nicotine - pharmacology; Peptide Fragments - metabolism; Plaque, Amyloid - drug effects; Plaque, Amyloid - pathology; Reactive Oxygen Species - metabolism; Receptors, Nicotinic - metabolism; Superoxide Dismutase - metabolism; Superoxide Dismutase-1
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.05-5214fje

Nicotine reduces β-amyloidosis and has a beneficial effect against Alzheimer's disease (AD), but the underlying mechanism is not clear. The abnormal interactions of β-amyloid (Aβ) with metal ions such as copper and zinc are implicated in the process of Aβ deposition in AD brains. In the present study, we investigated the effect of nicotine on metal homeostasis in the hippocampus and cortex of APPV⁷¹⁷I (London mutant form of APP) transgenic mice. A significant reduction in the metal contents of copper and zinc in senile plaques and neuropil is observed after nicotine treatment. The densities of copper and zinc distributions in a subfield of the hippocampus CA1 region are also reduced after nicotine treatment. We further studied the mechanism of nicotine-mediated effect on metal homeostasis by using SH-SY5Y cells overexpressing the Swedish mutant form of human APP (APPsw). Nicotine treatment decreases the intracellular copper concentration and attenuates Aβ-mediated neurotoxicity facilitated by the addition of copper, and these effects are independent of the activation of nicotinic acetylcholine-receptor. These data suggest that the effect of nicotine on reducing β-amyloidosis is partly mediated by regulating metal homeostasis.--Zhang, J., Liu, Q., Chen, Q., Liu, N.-Q., Li, F.-L., Lu, Z.-B., Qin, C., Zhu, H., Huang, Y.-Y., He, W., and Zhao, B.-L. Nicotine attenuates β-amyloid-induced neurotoxicity by regulating metal homeostasis.