Nicotine attenuates beta-amyloid-induced neurotoxicity by regulating metal homeostasis.

Abstract

Nicotine reduces beta-amyloidosis and has a beneficial effect against Alzheimer's disease (AD), but the underlying mechanism is not clear. The abnormal interactions of beta-amyloid (Abeta) with metal ions such as copper and zinc are implicated in the process of Abeta deposition in AD brains. In the present study, we investigated the effect of nicotine on metal homeostasis in the hippocampus and cortex of APP(V717I) (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 Abeta-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 beta-amyloidosis is partly mediated by regulating metal homeostasis.

• Authors: Jie Zhang, Qiang Liu, Qi Chen, Nian-Qing Liu, Fu-Liang Li, Zhong-Bing Lu, Chuan Qin, Hua Zhu, Yu-Ying Huang, Wei He, Bao-Lu Zhao
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 20 Issue 8 Pg. 1212-4 (Jun 2006) ISSN: 1530-6860 [Electronic] United States
• PMID: 16627626 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Amyloid beta-Protein Precursor
• Ccs protein, mouse
• Metals
• Molecular Chaperones
• Neuroprotective Agents
• Peptide Fragments
• Reactive Oxygen Species
• Receptors, Nicotinic
• SOD1 protein, human
• amyloid beta-protein (1-40)
• Nicotine
• Copper
• Sod1 protein, mouse
• Superoxide Dismutase
• Superoxide Dismutase-1

Topics

• Amyloid beta-Peptides (metabolism)
• Amyloid beta-Protein Precursor (genetics, metabolism)
• Amyloidosis (metabolism, pathology)
• Animals
• Cell Survival (drug effects)
• Copper (antagonists & inhibitors, metabolism, pharmacology)
• Hippocampus (drug effects, metabolism, pathology)
• Homeostasis
• Humans
• Metals (metabolism)
• Mice
• Mice, Transgenic
• Molecular Chaperones (metabolism)
• Neuroprotective Agents (pharmacology)
• Nicotine (pharmacology)
• Peptide Fragments (metabolism)
• Plaque, Amyloid (drug effects, pathology)
• Reactive Oxygen Species (metabolism)
• Receptors, Nicotinic (metabolism)
• Superoxide Dismutase (metabolism)
• Superoxide Dismutase-1