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Issue 9, 2017
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The double-edged role of copper in the fate of amyloid beta in the presence of anti-oxidants

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Abstract

The biological fate of amyloid beta (Aβ) species is a fundamental question in Alzheimer’s disease (AD) pathogenesis. The competition between clearance and aggregation of Aβs is critical for the onset of AD. Copper has been widely considered to be an inducer of harmful crosslinking of Aβs, and an important triggering factor for the onset of AD. In this report, however, we present data to show that copper can also be an inducer of Aβ degradation in the presence of a large excess of well-known intrinsic (such as dopamine) or extrinsic (such as vitamin C) anti-oxidants. The degraded fragments were identified using SDS-Page gels, and validated via nanoLC-MS/MS. A tentative mechanism for the degradation was proposed and validated with model peptides. In addition, we performed electrophysiological analysis to investigate the synaptic functions in brain slices, and found that in the presence of a significant excess of vitamin C, Cu(II) could prevent an Aβ-induced deficit in synaptic transmission in the hippocampus. Collectively, our evidence strongly indicated that a proper combination of copper and anti-oxidants might have a positive effect on the prevention of AD. This double-edged function of copper in AD has been largely overlooked in the past. We believe that our report is very important for fully understanding the function of copper in AD pathology.

Graphical abstract: The double-edged role of copper in the fate of amyloid beta in the presence of anti-oxidants

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Publication details

The article was received on 21 Apr 2017, accepted on 19 Jun 2017 and first published on 22 Jun 2017


Article type: Edge Article
DOI: 10.1039/C7SC01787A
Citation: Chem. Sci., 2017,8, 6155-6164
  • Open access: Creative Commons BY license
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    The double-edged role of copper in the fate of amyloid beta in the presence of anti-oxidants

    J. Yang, X. Zhang, Y. Zhu, E. Lenczowski, Y. Tian, J. Yang, C. Zhang, M. Hardt, C. Qiao, R. E. Tanzi, A. Moore, H. Ye and C. Ran, Chem. Sci., 2017, 8, 6155
    DOI: 10.1039/C7SC01787A

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