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International Journal of Alzheimer’s Disease
Volume 2011 (2011), Article ID 607861, 7 pages
Research Article

Correlation of Copper Interaction, Copper-Driven Aggregation, and Copper-Driven H2O2 Formation with Aβ40 Conformation

1Institute of Life Science, Tzu Chi University, Hualien 970, Taiwan
2Department of Physics, National Dong Hwa University, Hualien 974, Taiwan
3Institute of Pharmacology, National Yang-Ming University, Shihpai, Taipei 112, Taiwan
4Institute of Molecular Biology, National Chung-Cheng University, Chiayi 621, Taiwan
5Department of Biochemistry and Molecular Biology, National Yang-Ming University, Shihpai, Taipei 112, Taiwan
6Department of Medical Research & Education, Taipei Veterans General Hospital, Shihpai, Taipei 112, Taiwan
7Department of Medicine, Mackay Medical College, Taipei County 252, Taiwan

Received 15 September 2010; Accepted 15 November 2010

Academic Editor: Craig Atwood

Copyright © 2011 Chia-Anne Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The neurotoxicity of Aβ is associated with the formation of free radical by interacting with redox active metals such as Cu2+. However, the relationship between ion-interaction, ion-driven free radical formation, and Aβ conformation remains to be further elucidated. In the present study, we investigated the correlation of Cu2+ interaction and Cu2+-driven free radical formation with Aβ40 conformation. The Cu2+-binding affinity for Aβ40 in random coiled form is 3-fold higher than that in stable helical form. Unexpectedly but interestingly, we demonstrate in the first time that the stable helical form of Aβ40 can induce the formation of H2O2 by interacting with Cu2+. On the other hand, the H2O2 generation is repressed at Aβ/Cu2+ molar ratio ≥1 when Aβ40 adopts random coiled structure. Taken together, our result demonstrates that Aβ40 adopted a helical structure that may play a key factor for the formation of free radical with Cu2+ ions.