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Issue 11, 2013
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The effect of Cu2+ and Zn2+ on the Aβ42 peptide aggregation and cellular toxicity

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Abstract

The coordination chemistry of Cu and Zn metal ions with the amyloid β (Aβ) peptides has attracted a lot of attention in recent years due to its implications in Alzheimer's disease. A number of reports indicate that Cu and Zn have profound effects on Aβ aggregation. However, the impact of these metal ions on Aβ oligomerization and fibrillization is still not well understood, especially for the more rapidly aggregating and more neurotoxic Aβ42 peptide. Here we report the effect of Cu2+ and Zn2+ on Aβ42 oligomerization and aggregation using a series of methods such as Thioflavin T (ThT) fluorescence, native gel and Western blotting, transmission electron microscopy (TEM), and cellular toxicity studies. Our studies suggest that both Cu2+ and Zn2+ ions inhibit Aβ42 fibrillization. While presence of Cu2+ stabilizes Aβ42 oligomers, Zn2+ leads to formation of amorphous, non-fibrillar aggregates. The effects of temperature, buffer, and metal ion concentration and stoichiometry were also studied. Interestingly, while Cu2+ increases the Aβ42-induced cell toxicity, Zn2+ causes a significant decrease in Aβ42 neurotoxicity. While previous reports have indicated that Cu2+ can disrupt β-sheets and lead to non-fibrillar Aβ aggregates, the neurotoxic consequences were not investigated in detail. The data presented herein including cellular toxicity studies strongly suggest that Cu2+ increases the neurotoxicity of Aβ42 due to stabilization of soluble Aβ42 oligomers.

Graphical abstract: The effect of Cu2+ and Zn2+ on the Aβ42 peptide aggregation and cellular toxicity

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Publication details

The article was received on 30 maí 2013, accepted on 23 ágú. 2013 and first published on 23 ágú. 2013


Article type: Paper
DOI: 10.1039/C3MT00161J
Citation: Metallomics, 2013,5, 1529-1536
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    The effect of Cu2+ and Zn2+ on the Aβ42 peptide aggregation and cellular toxicity

    A. K. Sharma, S. T. Pavlova, J. Kim, J. Kim and L. M. Mirica, Metallomics, 2013, 5, 1529
    DOI: 10.1039/C3MT00161J

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