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Issue 7, 2013
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Selenoprotein P and selenoprotein M block Zn2+-mediated Aβ42 aggregation and toxicity

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Abstract

Aggregation and cytotoxicity of the amyloid-β (Aβ) peptide with transition metal ions in neuronal cells have been suggested to be involved in the progression of Alzheimer's disease (AD). A therapeutic strategy to combat this incurable disease is to design chemical agents to target metal–Aβ species. Selenoproteins are a group of special proteins that contain the 21st amino acid Sec in their sequence. Due to the presence of Sec, studies of this group of proteins are basically focused on their roles in regulating redox potential and scavenging reactive oxygen species. Here, we reported that the His-rich domain of selenoprotein P (SelP-H) and the Sec-to-Cys mutant selenoprotein M (SelM′) are capable of binding transition metal ions and modulating the Zn2+-mediated Aβ aggregation, ROS production and neurotoxicity. SelM′ (U48C) and SelP-H were found to coordinate 0.5 and 2 molar equivalents of Zn2+/Cd2+ with micromolar and submicromolar affinities, respectively. Metal binding induced the structural changes in SelP-H and SelM′ according to the circular dichorism spectra. Zn2+ binding to Aβ42 almost completely suppressed Aβ42 fibrillization, which could be significantly restored by SelP-H and SelM′, as observed by thioflavin T (ThT) fluorescence and transmission electron microscopy (TEM). Interestingly, both SelP-H and SelM′ inhibited Zn2+–Aβ42-induced neurotoxicity and the intracellular ROS production in living cells. These studies suggest that SelP and SelM may play certain roles in regulating redox balance as well as metal homeostasis.

Graphical abstract: Selenoprotein P and selenoprotein M block Zn2+-mediated Aβ42 aggregation and toxicity

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Publication details

The article was received on 31 Dec 2012, accepted on 16 Apr 2013 and first published on 17 Apr 2013


Article type: Paper
DOI: 10.1039/C3MT20282H
Metallomics, 2013,5, 861-870

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    Selenoprotein P and selenoprotein M block Zn2+-mediated Aβ42 aggregation and toxicity

    X. Du, H. Li, Z. Wang, S. Qiu, Q. Liu and J. Ni, Metallomics, 2013, 5, 861
    DOI: 10.1039/C3MT20282H

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