期刊
INORGANIC CHEMISTRY
卷 50, 期 5, 页码 1614-1618出版社
AMER CHEMICAL SOC
DOI: 10.1021/ic100967s
关键词
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资金
- Alzheimer's Association [IIRG-07-58211]
- Howard Hughes Medical Institute [52005900]
- NIH MARC [T34 08663]
The role of metal ions in Alzheimer's disease etiology is unresolved. For the redox-active metal ions iron and copper, the formation of reactive oxygen species by metal amyloid complexes has been proposed to contribute to Alzheimer's disease neurodegeneration. For copper, reactive oxygen species are generated by copper redox cycling between its 1+ and 2+ oxidation states. Thus, the A beta Cu-I complex is potentially a critical reactant associated with Alzheimer's disease etiology. Through competitive chelation, we have measured the affinity of the soluble copper-binding domain of the amyloid-beta peptide for Cu-I. The dissociation constants are in the femtomolar range for both wild-type and histidine-to-alanine mutants. These results indicate that Cu-I binds more tightly to monomeric amyloid-beta than Cu-II does, which leads us to propose that Cu-I is a relevant in vivo oxidation state.
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