{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:44:10Z","timestamp":1792802650404,"version":"4.5.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1994,4,12]]},"abstract":"<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>","DOI":"10.1073\/pnas.91.8.3270","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T09:08:01Z","timestamp":1149066481000},"page":"3270-3274","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":865,"title":["A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease."],"prefix":"10.1073","volume":"91","author":[{"given":"K","family":"Hensley","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Kentucky, Lexington 40506."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J M","family":"Carney","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Kentucky, Lexington 40506."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M P","family":"Mattson","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Kentucky, Lexington 40506."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Aksenova","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Kentucky, Lexington 40506."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Harris","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Kentucky, Lexington 40506."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J F","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Kentucky, Lexington 40506."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R A","family":"Floyd","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Kentucky, Lexington 40506."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D A","family":"Butterfield","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Kentucky, Lexington 40506."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1994,4,12]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.91.8.3270","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:14:41Z","timestamp":1649859281000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.91.8.3270"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,4,12]]},"references-count":0,"journal-issue":{"issue":"8","published-print":{"date-parts":[[1994,4,12]]}},"alternative-id":["10.1073\/pnas.91.8.3270"],"URL":"https:\/\/doi.org\/10.1073\/pnas.91.8.3270","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,4,12]]},"assertion":[{"value":"1994-04-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}