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First evidence for helical transitions in supercoiled DNA by amyloid Beta Peptide (1-42) and aluminum: a new insight in understanding Alzheimer's disease.

Muralidhar, L. Hegde and Anitha, Suram and Latha, Kallur S and Mustak, Mohammed S and Stein, Reuven and Ravid, R. and Jagannatha Rao, K. S. (2004) First evidence for helical transitions in supercoiled DNA by amyloid Beta Peptide (1-42) and aluminum: a new insight in understanding Alzheimer's disease. Journal of Molecular Neuroscience, 22 (1-2). pp. 19-31. ISSN 0895-8696

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Abstract

Previously, we evidenced a B --> Z helical change in Alzheimer's brain genomic DNA, leading to a hypothesis that Alzheimer's disease (AD) etiological factors such as aluminum (Al), amyloid beta (Abeta) peptide, and Tau might play a role in modulating DNA topology. In the present study, we investigated the interaction of Al and Abeta with DNA. Our results show that Abeta(1-42) could induce a B --> Psi (Psi) conformational change in pUC 18 supercoiled DNA (scDNA), Abeta(1-16) caused an altered B-form, whereas Al induced a complex B-C-A mixed conformation. Ethidium bromide binding and agarose gel electrophoresis studies revealed that Al uncoiled the DNAto a fully relaxed form, whereas Abeta(1-42) and Abeta(1-16) effected a partial uncoiling and also showed differential sensitivity toward chloroquine-induced topoisomer separation. Our findings show for the first time that Abeta and Al modulate both helicity and superhelicity in scDNA. A new hypothetical model explaining the potential toxicity of Abeta and Al in terms of their DNA binding properties leading to DNA conformational alteration is proposed.

Item Type: Article
Uncontrolled Keywords: Alzheimer’s disease; pUC18 supercoiled DNA; helical transitions; topoisomer separation; B-DNA; Z-DNA; ψ-DNA
Subjects: 500 Natural Sciences and Mathematics > 07 Life Sciences > 02 Evolution & genetics
Depositing User: Users 197 not found.
Date Deposited: 07 Jun 2011 10:58
Last Modified: 10 Oct 2018 11:08
URI: http://ir.cftri.com/id/eprint/2044

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