Generation of soluble oligomeric β-amyloid species via copper catalyzed oxidation with implications for Alzheimer's disease: A DFT study

Fredrik Haeffner (1, 2) , Kevin J. Barnham (3) , Ashley I. Bush (4) , Tore Brinck (1)

1 Physical Chemistry, Royal Institute of Technology
2 Chemical Science and Technology Laboratory, National Institute of Standards and Technology
3 Department of Pathology
4 Laboratory for Oxidation Biology, Genetics and Aging Research Unit and Department of Psychiatry

A mechanism for the oxidation of a dimeric β-amyloid copper ion complex is proposed based on DFT calculations. It involves the Met35 residue, which is believed to be important in the neurotoxicity causing Alzheimer's disease. Oxidation of Met35 is found to proceed readily with dioxygen when two Met35 residues are close to each other and the copper ion. This indicates that oxidants, such as hydrogen peroxide, are not necessary for oxidation of β-amyloid copper ion complexes. Understanding these processes could be pivotal in gaining more knowledge of this complex disease and for the development of therapeutic treatments.

Mots clés: Alzheimer's disease; β-amyloid; Copper ion; Met35; Molecular modeling; Oxidation

Fredrik Haeffner, Kevin J. Barnham, Ashley I. Bush, Tore Brinck. Generation of soluble oligomeric β-amyloid species via copper catalyzed oxidation with implications for Alzheimer's disease: A DFT study. Journal of Molecular Modeling, 2009, 16 (6), pp.1103-1108. ⟨10.1007/s00894-009-0619-6⟩. ⟨hal-00568335⟩