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.
|Number of pages||9|
|Journal||Brain Research Bulletin|
|State||Published - Sep 15 1999|
Bibliographical noteFunding Information:
This work was supported in part by National Institutes of Health grants (nos. AG-05119 and AG-10836).
- Electron paramagnetic resonance (EPR)
- Phenyl-tert-butylnitrone (PBN)
- Protein Oxidation
- Reactive oxygen species (ROS)
- Spin trapping
ASJC Scopus subject areas
- Neuroscience (all)