title: Studies on the mechanism of the DNA nicking property of amyloid-β40: implications in Alzheimer's disease.
abstract: Amyloid-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.
authors.affiliation: Centre of Excellence for Alzheimer's Disease Research & Care, School of Exercise Biomedical and Health Sciences, Edith Cowan University, WA, Australia.
authors.forename: Veer B
authors.initials: VB
authors.lastname: Gupta
authors.forename: Florence S
authors.initials: FS
authors.lastname: Monica
authors.forename: Ruben
authors.initials: R
authors.lastname: Berrocal
authors.forename: K Subba
authors.initials: KS
authors.lastname: Rao
authors.forename: K S Jagannatha
authors.initials: KS
authors.lastname: Rao
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000235:genetics* / Q000378:metabolism*; D053904:DNA Breaks, Single-Stranded; D004249:DNA Damage / Q000235:genetics; D018450:Disease Progression; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40)