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

作者：Haeffner Fredrik; Barnham Kevin J; Bush Ashley I; Brinck Tore^*

来源：Journal of Molecular Modeling, 2010, 16(6): 1103-1108.

DOI：10.1007/s00894-009-0619-6

• Alzheimer's disease
• beta-amyloid
• Copper ion
• Met35
• Molecular modeling
• Oxidation

A mechanism for the oxidation of a dimeric beta-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 beta-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.

• 出版日期2010-6