eCite Digital Repository

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

Citation

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]


Preview
PDF
1Mb
  

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

Official URL: http://www.plosone.org/article/info%3Adoi%2F10.137...

DOI: doi:10.1371/journal.pone.0012030

Abstract

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:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Chung, RS (Associate Professor Roger Chung)
Author:Howells, C (Ms Claire Howells)
Author:Eaton, ED (Dr Emma Eaton)
Author:Shabala, L (Dr Lana Shabala)
Author:Woodhouse, A (Dr Adele Woodhouse)
Author:Bennett, WR (Dr Bill Bennett)
Author:Ray, S (Mrs Shannon Huskins)
Author:Vickers, JC (Professor James Vickers)
Author:West, AK (Professor Adrian West)
ID Code:65120
Year Published:2010
Web of Science® Times Cited:40
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-10-05
Last Modified:2011-05-05
Downloads:338 View Download Statistics

Repository Staff Only: item control page