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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.

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Relation http://ir.cftri.com/2044/
JMN-02-04
 
Title First evidence for helical transitions in supercoiled DNA by amyloid Beta Peptide (1-42) and aluminum: a new insight in understanding Alzheimer's disease.
 
Creator Muralidhar, L. Hegde
Anitha, Suram
Latha, Kallur S
Mustak, Mohammed S
Stein, Reuven
Ravid, R.
Jagannatha Rao, K. S.
 
Subject 02 Evolution & genetics
 
Description 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.
 
Date 2004
 
Type Article
PeerReviewed
 
Format application/pdf
 
Language en
 
Identifier http://ir.cftri.com/2044/1/Journal_of_Molecular_Neuroscience_2004_22_19-.pdf
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