A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease.
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- K Hensley
- Department of Chemistry, University of Kentucky, Lexington 40506.
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- J M Carney
- Department of Chemistry, University of Kentucky, Lexington 40506.
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- M P Mattson
- Department of Chemistry, University of Kentucky, Lexington 40506.
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- M Aksenova
- Department of Chemistry, University of Kentucky, Lexington 40506.
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- M Harris
- Department of Chemistry, University of Kentucky, Lexington 40506.
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- J F Wu
- Department of Chemistry, University of Kentucky, Lexington 40506.
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- R A Floyd
- Department of Chemistry, University of Kentucky, Lexington 40506.
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- D A Butterfield
- Department of Chemistry, University of Kentucky, Lexington 40506.
抄録
<jats:p>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.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 91 (8), 3270-3274, 1994-04-12
Proceedings of the National Academy of Sciences
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詳細情報
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- CRID
- 1363388845711536384
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- NII論文ID
- 30016298918
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- ISSN
- 10916490
- 00278424
- http://id.crossref.org/issn/00278424
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