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PLoS One. 2010 Aug 11;5(8):e12030. doi: 10.1371/journal.pone.0012030.

The native copper- and zinc-binding protein metallothionein blocks copper-mediated Abeta aggregation and toxicity in rat cortical neurons.

Author information

1
NeuroRepair Group, Menzies Research Institute, University of Tasmania, Hobart, Australia. Roger.Chung@utas.edu.au

Abstract

BACKGROUND:

A major pathological hallmark of AD is the deposition of insoluble extracellular beta-amyloid (Abeta) plaques. There are compelling data suggesting that Abeta aggregation is catalysed by reaction with the metals zinc and copper.

METHODOLOGY/PRINCIPAL FINDINGS:

We now report that the major human-expressed metallothionein (MT) subtype, MT-2A, is capable of preventing the in vitro copper-mediated aggregation of Abeta1-40 and Abeta1-42. This action of MT-2A appears to involve a metal-swap between Zn7MT-2A and Cu(II)-Abeta, since neither Cu10MT-2A or carboxymethylated MT-2A blocked Cu(II)-Abeta aggregation. Furthermore, Zn7MT-2A blocked Cu(II)-Abeta induced changes in ionic homeostasis and subsequent neurotoxicity of cultured cortical neurons.

CONCLUSIONS/SIGNIFICANCE:

These results indicate that MTs of the type represented by MT-2A are capable of protecting against Abeta aggregation and toxicity. Given the recent interest in metal-chelation therapies for AD that remove metal from Abeta leaving a metal-free Abeta that can readily bind metals again, we believe that MT-2A might represent a different therapeutic approach as the metal exchange between MT and Abeta leaves the Abeta in a Zn-bound, relatively inert form.

PMID:
20711450
PMCID:
PMC2920313
DOI:
10.1371/journal.pone.0012030
[Indexed for MEDLINE]
Free PMC Article

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