Methionine residue 35 is important in amyloid β-peptide-associated free radical oxidative stress

Sridhar Varadarajan, Servet Yatin, Jaroslaw Kanski, Feerozeh Jahanshahi, D. Allan Butterfield

Research output: Contribution to journalArticlepeer-review

168 Scopus citations

Abstract

Amyloid β-peptide (Aβ), the central constituent of senile plaques in Alzheimer's disease (AD) brain, has been shown to be a source of free radical oxidative stress that may lead to neurodegeneration. In the current study Aβ(1-40), found in AD brain, and the amyloid fragment Aβ(25-35) were used in conjunction with electron paramagnetic resonance spin trapping techniques to demonstrate that these peptides mediate free radical production. The methionine residue in these peptides is believed to play an important role in their neurotoxicity. Substitution of methionine by structurally similar norleucine in both Aβ(1-40) and Aβ(25-35), and the substitution of methionine by valine, or the removal of the methionine in Aβ(25-35), abrogates free radical production and protein oxidation of and toxicity to hippocampal neurons. These results are discussed with relevance to the hypothesis that neurodegeneration in Alzheimer's disease may be due in part to Aβ-associated free radical oxidative stress that involves methionine, and to the use of spin trapping methods to infer mechanistic information about Aβ. Copyright (C) 1999 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)133-141
Number of pages9
JournalBrain Research Bulletin
Volume50
Issue number2
DOIs
StatePublished - Sep 15 1999

Bibliographical note

Funding Information:
This work was supported in part by National Institutes of Health grants (nos. AG-05119 and AG-10836).

Keywords

  • Electron paramagnetic resonance (EPR)
  • Neurotoxicity
  • Phenyl-tert-butylnitrone (PBN)
  • Protein Oxidation
  • Reactive oxygen species (ROS)
  • Spin trapping

ASJC Scopus subject areas

  • General Neuroscience

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