Methionine residue 35 is critical for the oxidative stress and neurotoxic properties of Alzheimer's amyloid β-peptide 1-42

D. Allan Butterfield, Jaroslaw Kanski

Research output: Contribution to journalArticlepeer-review

141 Scopus citations

Abstract

Amyloid β-peptide 1-42 [Aβ(1-42)] is central to the pathogenesis of Alzheimer's disease (AD), and the AD brain is under intense oxidative stress. Our laboratory combined these two aspects of AD into the Aβ-associated free radical oxidative stress model for neurodegeneration in AD brain. Aβ(1-42) caused protein oxidation, lipid peroxidation, reactive oxygen species formation, and cell death in neuronal and synaptosomal systems, all of which could be inhibited by free radical antioxidants. Recent studies have been directed at discerning molecular mechanisms by which Aβ(1-42)-associated free radical oxidative stress and neurotoxicity arise. The single methionine located in residue 35 of Aβ(1-42) is critical for these properties. This review presents the evidence supporting the role of methionine in Aβ(1-42)-associated free radical oxidative stress and neurotoxicity. This work is of obvious relevance to AD and provides a coupling between the centrality of Aβ(1-42) in the pathogenesis of AD and the oxidative stress under which the AD brain exists.

Original languageEnglish
Pages (from-to)1299-1309
Number of pages11
JournalPeptides
Volume23
Issue number7
DOIs
StatePublished - 2002

Bibliographical note

Funding Information:
Professor Butterfield thanks his former graduate students and postdoctoral fellows, especially Sridhar Varadarajan, Servet Yatin, Tanuja Koppal, Ramachandran Subramaniam, and Kenneth Hensley for the excellent research that led to this review. We thank Jennifer Drake for assistance with the figures of this manuscript. This work was supported in part by NIH (NIA) grants to D.A.B.

Keywords

  • Amyloid
  • Methionine
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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