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- Title
Resistance of Cu(Aβ4-16) to Copper Capture by Metallothionein-3 Supports a Function for the Aβ4-42 Peptide as a Synaptic Cu<sup>II</sup> Scavenger.
- Authors
Wezynfeld, Nina E.; Stefaniak, Ewelina; Stachucy, Kinga; Drozd, Agnieszka; Płonka, Dawid; Drew, Simon C.; Krężel, Artur; Bal, Wojciech
- Abstract
Aβ4-42 isamajor species of Aβ peptide in the brains of both healthy individuals and those affected by Alzheimer's disease. It has recently been demonstrated to bind CuII with an affinity approximately 3000 times higher than the commonly studied Aβ1-42 and Aβ1-40 peptides, which are implicated in the pathogenesis of Alzheimer's disease. Metallothionein-3, a protein considered to orchestrate copper and zinc metabolism in the brain and provide antioxidant protection, was shown to extract CuII from Aβ1-40 when acting in its native Zn7MT-3 form. This reaction is assumed to underlie the neuroprotective effect of Zn7MT-3 against Aβ toxicity. In this work, we used the truncated model peptides Aβ1-16 and Aβ4- 16 to demonstrate that the high-affinity CuII complex of Aβ4-16 is resistant to Zn7MT-3 reactivity. This indicates that the analogous complex of the full-length peptide Cu(Aβ4-42) will not yield copper to MT-3 in the brain, thus supporting the concept of a physiological role for Aβ4-42 as a CuII scavenger in the synaptic cleft.
- Subjects
COPPER spectra; METALLOTHIONEIN; PEPTIDES; ALZHEIMER'S disease; ZINC metabolism; COPPER metabolism; NEUROPROTECTIVE agents
- Publication
Angewandte Chemie, 2016, Vol 128, Issue 29, p8375
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201511968