Home >> Letters in Peptide Science, Volume 10, Number 5

Methionine oxidation: Implications for the mechanism of toxicity of the beta-amyloid peptide from Alzheimer’s disease

Authors: Giuseppe D. Ciccotosto1; Kevin J. Barnham2; Robert A. Cherny2; Colin L. Masters2; Ashley I. Bush3; Cyril C. Curtain4; Roberto Cappai2; Deborah Tew2

Source: Letters in Peptide Science, Volume 10, Number 5, 2003 , pp. 413-417(5)

Publisher: Springer

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Abstract:

The amyloid beta-peptide, Abeta is toxic to neurons and this toxicity plays a central role in the progression of Alzheimer’s disease. The mechanism(s) by which Abeta exerts its toxicity has been hotly debated with several theories postulated. Here we discuss the role of oxidation of the sulfur atom of Met35 in Abeta42 (Met(O)Abeta), a modification that has significant implications for the mechanism of Abeta toxicity. Both Met(O)Abeta and its native form display toxicity to primary neuronal cells in culture which can be rescued by catalase, a H2O2 inhibitor and clioquinol a mild copper chelator. However both native Abeta and Met(O)Abeta differ substantially in primary and secondary structures, solubility, ability to penetrate lipid membranes, and oligomerization profiles. It is clearly evident that metals play an important role in the oxidation of Abeta to Met(O)Abeta via Fenton chemistry and that regulation of this pathway has a potential therapeutic application for the regulation of Alzheimer’s disease.

Keywords: Alzheimer’s disease; amyloid beta; copper; oxidation; toxicity

Document Type: Research article

DOI: http://dx.doi.org/10.1007/s10989-004-2394-7

Affiliations: 1: Department of Pathology, The University of Melbourne, The Mental Health Research Institute of Victoria, Victoria, Parkville, Victoria 3010, 3052, Australia (), Email: jcicco@unimelb.edu.au 2: Department of Pathology, The University of Melbourne, The Mental Health Research Institute of Victoria, Victoria, Parkville, Victoria 3010, 3052, Australia 3: Department of Pathology, The University of Melbourne, The Mental Health Research Institute of Victoria, Victoria, Parkville, Victoria 3010, 3052, Australia; y for Oxidation Biology, Genetics and Aging Unit and Department of Psychiatry, Laborator, 4: Department of Pathology, The University of Melbourne, The Mental Health Research Institute of Victoria, Victoria, Parkville, Victoria 3010, 3052, Australia; School of Physics and Materials Engineering, Monash University, VictoriaAustralia

Publication date: 2003-01-01

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