Table of Contents
Journal of Amino Acids
Volume 2011, Article ID 198430, 10 pages
http://dx.doi.org/10.4061/2011/198430
Review Article

Methionine-35 of Aβ(1–42): Importance for Oxidative Stress in Alzheimer Disease

1Department of Chemistry, University of Kentucky, Lexington, KY 40506-0055, USA
2Center of Membrane Sciences, University of Kentucky, Lexington, KY 40506-0055, USA
3Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40506-0055, USA

Received 1 January 2011; Accepted 14 April 2011

Academic Editor: Andreas Wyttenbach

Copyright © 2011 D. Allan Butterfield and Rukhsana Sultana. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Alzheimer disease (AD) is an age-related progressive neurodegenerative disorder. This devastating disease is characterized by the presence of senile plaques (SP), neurofibrillary tangles (NFTs), and loss of synapses. Amyloid beta-peptide 1–42 (Aβ(1–42)) is the main component of SP and is pivotal to AD pathogenesis. Brain of subjects with AD and arguably its earliest manifestation, mild cognitive impairment (MCI), demonstrate increased levels of oxidative stress markers. Our laboratory combined these two aspects of AD and MCI and proposed the Aβ(1–42)-associated free radical oxidative stress hypothesis to explain oxidative stress under which the MCI and AD brain exist and the loss of synapses in both disorders. A large number of in vitro and in vivo studies showed that Aβ causes protein oxidation, lipid peroxidation, reactive oxygen species formation, and cell death in neuronal and synaptosomal systems. Methionine located at residue 35 of Aβ(1–42) is an important contributor to the oxidative stress associated with this neurotoxic peptide. In this paper, we summarize studies involving Met-35 of Aβ(1–42). Understanding the role of the single methionine residue of Aβ(1–42) may help in understanding underlying disease mechanisms in AD and MCI.