Resistance of Cu(Aβ4–16) to Copper Capture by Metallothionein-3 Supports a Function for the Aβ4–42 Peptide as a Synaptic CuIIScavenger

Abstract

Aβ4-42 is a major 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 CuIIwith 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 CuIIfrom 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..