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Studies on the mechanism of the DNA nicking property of amyloid-β40: Implications in Alzheimer's disease
journal contribution
posted on 2022-12-01, 02:48 authored by K S J Rao, Veer GuptaVeer Gupta, F S Monica, R Berrocal, K S RaoAmyloid-β peptide is presumably a key etiological factor involved in the pathogenesis of Alzheimer's disease (AD), and several hypotheses exist on the possible ways Aβ contributes to the progression of the disease. There are reports on the nuclear localization of Aβ and very limited evidence on its DNA binding property. The present study provided the mechanism of Aβ enantiomers binding to DNA and showed that Aβ40L induces ψ-DNA, while Aβ40D causes only altered B-DNA. Further, we evidenced the DNA nicking property of Aβ enantiomers and endonuclease mimicking behavior. The role of Aβ in modulating DNA stability was reported by altered melting temperature and ethidium bromide binding studies. The data provides new evidence on stereospecific dependent Aβ-DNA interaction and we discuss its biological relevance to neurodegeneration. Our results imply that Aβ-DNA interaction needs to be considered as a significant cause of the toxicity in the pathogenesis of AD. © 2013 - IOS Press and the authors. All rights reserved.
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Journal
Journal of Alzheimer's DiseaseVolume
33Pagination
1059 - 1071Publisher DOI
ISSN
1387-2877eISSN
1875-8908Publication classification
C1.1 Refereed article in a scholarly journalUsage metrics
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