The critical role of methionine 35 in Alzheimer's amyloid β-peptide (1-42)-induced oxidative stress and neurotoxicity

D. Allan Butterfield, Debra Boyd-Kimball

Research output: Contribution to journalReview articlepeer-review

247 Scopus citations

Abstract

Amyloid beta-peptide (1-42) [Aβ(1-42)] has been proposed to play a central role in the pathogenesis of Alzheimer's disease, a neurodegenerative disorder associated with cognitive decline and aging. AD brain is under extensive oxidative stress, and Aβ(1-42) has been shown to induce protein oxidation, lipid peroxidation, and reactive oxygen species formation in neurons and synaptosomes, all of which are inhibited by the antioxidant vitamin E. Additional studies have shown that Aβ(1-42) induces oxidative stress when expressed in vivo in Caenorhabditis elegans, but when methionine 35 is replaced by cysteine, the oxidative stress is attenuated. This finding coupled with in vitro studies using mutant peptides have demonstrated a critical role for methionine 35 in the oxidative stress and neurotoxic properties of Aβ(1-42). In this review, we discuss the role of methionine 35 in the oxidative stress and neurotoxicity induced by Aβ(1-42) and the implications of these findings in the pathogenesis of AD.

Original languageEnglish
Pages (from-to)149-156
Number of pages8
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1703
Issue number2
DOIs
StatePublished - Jan 17 2005

Bibliographical note

Funding Information:
This work was supported by NIH grants AG-05119 and AG-10836.

Keywords

  • Alzheimer's disease
  • Amyloid beta-peptide
  • Methionine
  • Oxidative stress
  • including protein oxidation and lipid peroxidation

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

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