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The Native Copper- and Zinc- Binding Protein Metallothionein Blocks Copper-Mediated Aβ Aggregation and Toxicity in Rat Cortical Neurons


Chung, RS and Howells, C and Eaton, ED and Shabala, L and Zovo, K and Palumaa, P and Sillard, R and Woodhouse, A and Bennett, WR and Ray, S and Vickers, JC and West, AK, The Native Copper- and Zinc- Binding Protein Metallothionein Blocks Copper-Mediated Aβ Aggregation and Toxicity in Rat Cortical Neurons, P L o S One, 5, (8) EJ ISSN 1932-6203 (2010) [Refereed Article]


Copyright Statement

Copyright © 2010 Chung et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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DOI: doi:10.1371/journal.pone.0012030


Background: A major pathological hallmark of AD is the deposition of insoluble extracellular b-amyloid (Ab) plaques. There are compelling data suggesting that Ab 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 Ab1–40 and Ab1–42. This action of MT-2A appears to involve a metal-swap between Zn7MT-2A and Cu(II)-Ab, since neither Cu10MT-2A or carboxymethylated MT-2A blocked Cu(II)-Ab aggregation. Furthermore, Zn7MT-2A blocked Cu(II)-Ab 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 Ab aggregation and toxicity. Given the recent interest in metal-chelation therapies for AD that remove metal from Ab leaving a metal-free Ab that can readily bind metals again, we believe that MT-2A might represent a different therapeutic approach as the metal exchange between MT and Ab leaves the Ab in a Zn-bound, relatively inert form.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Chung, RS (Associate Professor Roger Chung)
UTAS Author:Howells, C (Ms Claire Howells)
UTAS Author:Eaton, ED (Dr Emma Eaton)
UTAS Author:Shabala, L (Associate Professor Lana Shabala)
UTAS Author:Woodhouse, A (Dr Adele Woodhouse)
UTAS Author:Bennett, WR (Dr Bill Bennett)
UTAS Author:Ray, S (Mrs Shannon Huskins)
UTAS Author:Vickers, JC (Professor James Vickers)
UTAS Author:West, AK (Professor Adrian West)
ID Code:65120
Year Published:2010
Web of Science® Times Cited:54
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-10-05
Last Modified:2011-05-05
Downloads:434 View Download Statistics

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