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A new evidence for DNA nicking property of amyloid beta-peptide(1–42): Relevance to Alzheimer’s disease

Suram, A. and Hegde, M. L. and Rao, K. S. J. (2007) A new evidence for DNA nicking property of amyloid beta-peptide(1–42): Relevance to Alzheimer’s disease. Archives of Biochemistry and Biophysics, 463. pp. 245-252.

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Abstract

Alzheimer’s disease (AD) is a complex neurodegenerative disorder with a progressive mental deterioration manifested by memory loss. No definite etiology has been established for AD to date. Amyloid beta (Ab) protein plays a central role in the pathology of AD through multiple pathways like oxidative stress, apoptosis etc. Recently, our laboratory first time has evidenced localization of Ab immunoreactivity in apoptotic nuclei of degenerating AD brain hippocampal neurons and also showed that Ab (1–42) binds and alters the helicity of DNA. The present study provided fundamental data on DNA nicking induced by Ab. The results showed that Ab (1–42) has DNA nicking activity similar to nucleases. Further, magnesium ion (1 mM) enhanced DNA nicking activity of Ab. The data on Ab solution stability on DNA nicking revealed that the oligomers of Ab (1–42) peptides showed more DNA nicking activity compared to monomers and fibrillar forms. The nuclease specific inhibitor aurintricarboxylic acid prevented the DNA nicking property of Ab. Transmission electron microscopy (TEM) studies revealed that Ab causes open circular and linear forms in supercoiled DNA and also clearly evidenced the physical association of protein–DNA complex. The above data indicated that Ab mimics endonuclease behavior. Our finding of DNA nicking activity of Ab peptides has biological significance in terms of causing direct DNA damage.

Item Type: Article
Uncontrolled Keywords: Alzheimer’s disease; Amyloid b; Supercoiled DNA; Thioflavine-T; Nicking; Transmission electron microscope
Subjects: 600 Technology > 01 Medical sciences
Divisions: Dept. of Biochemistry
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 20 Nov 2008 06:48
Last Modified: 18 Nov 2016 11:16
URI: http://ir.cftri.com/id/eprint/8849

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