A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease - PubMed (original) (raw)

A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease

K Hensley et al. Proc Natl Acad Sci U S A. 1994.

Abstract

beta-Amyloid is a 39- to 43-amino-acid neurotoxic peptide that aggregates to form the core of Alzheimer disease-associated senile (amyloid) plaques. No satisfactory hypothesis has yet been proposed to explain the mechanism of beta-amyloid aggregation and toxicity. We present mass spectrometric and electron paramagnetic resonance spin trapping evidence that beta-amyloid, in aqueous solution, fragments and generates free radical peptides. beta-Amyloid fragments, at concentrations that previously have been shown to be neurotoxic to cultured neurons, can inactivate oxidation-sensitive glutamine synthetase and creatine kinase enzymes. Also, salicylate hydroxylation assays indicate that reactive oxygen species are generated by the beta-amyloid-(25-35) fragment during cell-free incubation. These results are formulated into a free radical-based unifying hypothesis for neurotoxicity of beta-amyloid and are discussed with reference to membrane molecular alterations in Alzheimer disease.

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References

    1. Trends Neurosci. 1993 Oct;16(10):409-14 - PubMed
    1. Brain Res. 1993 Sep 3;621(1):35-49 - PubMed
    1. J Neurol Sci. 1980 Mar;45(2-3):323-30 - PubMed
    1. J Biol Chem. 1983 Oct 10;258(19):11823-7 - PubMed
    1. J Free Radic Biol Med. 1986;2(1):13-8 - PubMed

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