Open AccessCu(II) Potentiation of Alzheimer Aβ1‐40 Cytotoxicity and Transition on its Secondary Structure
Author(s) -
DAI XueLing,
SUN YaXuan,
JIANG ZhaoFeng
Publication year - 2006
Publication title -
acta biochimica et biophysica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.771
H-Index - 57
eISSN - 1745-7270
pISSN - 1672-9145
DOI - 10.1111/j.1745-7270.2006.00228.x
Subject(s) - chemistry , electron paramagnetic resonance , circular dichroism , copper , hydrogen peroxide , amyloid beta , amyloid (mycology) , biophysics , peptide , crystallography , inorganic chemistry , biochemistry , nuclear magnetic resonance , physics , organic chemistry , biology
Mounting evidence has shown that dyshomeostasis of the redox‐active biometals such as Cu and Fe can lead to oxidative stress, which plays a key role in the neuropathology of Alzheimer's disease (AD). Here we demonstrate that with the formation of Cu(II)‐A(31‐40 complexes, copper markedly potentiates the neurotoxicity exhibited by β‐amyloid peptide (Aβ). A greater amount of hydrogen peroxide was released when Cu(II)‐A(31‐40 complexes was added to the xanthine oxidase/xanthine system detected by potassium iodide spectrophotometry. Copper bound to Aβ1‐40 was observed by electron paramagnetic resonance (EPR) spectroscopy. Circular dichroism (CD) studies indicated that copper chelation could cause a structural transition of Aβ. The addition of copper to Aβ introduced an increase on β‐sheet as well as α‐helix, which may be responsible for the aggregation of Aβ. We hypothesized that Aβ aggregation induced by copper may be responsible for local injury in AD. The interaction between Cu 2+ and Aβ also provides a possible mechanism for the enrichment of metal ions in amyloid plaques in the AD brain. Edited by Ming‐Hua XU