Abstract
β-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 β- amyloid aggregation and toxicity. We present mass spectrometric and electron paramagnetic resonance spin trapping evidence that β-amyloid, in aqueous solution, fragments and generates free radical peptides. β-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 β-amyloid-(25-35) fragment during cell-free incubation. These results are formulated into a free radical-based unifying hypothesis for neurotoxicity of β-amyloid and are discussed with reference to membrane molecular alterations in Alzheimer disease.
Original language | English (US) |
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Pages (from-to) | 3270-3274 |
Number of pages | 5 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 91 |
Issue number | 8 |
State | Published - Apr 12 1994 |
Externally published | Yes |
Keywords
- enzyme inactivation
- membrane damage
- oxidative stress
- peptide fragmentation
- spin trapping
ASJC Scopus subject areas
- Genetics
- General