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Studies on Metal-DNA Interactions Induced DNA Conformations in Relevance to Neurological Disorders

Mohammed Shafiul, Mustak B (2006) Studies on Metal-DNA Interactions Induced DNA Conformations in Relevance to Neurological Disorders. PhD thesis, University of Mysore .

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Abstract

Trace metal ions play a very important role in biological processes. Trace elements are sub divided into three main categories: i) Essential, like Fe, Cu, Se, Zn, Mn, Cr, Mo, Co and I; ii) Beneficial but not currently thought to be essential including F, V, Br, and Li ; iii) Toxic metals like Pb, Cd, Hg and Al. Trace metal homeostasis is essential for normal biological functions and any change in homeostasis leads to pathophysiology of cells. Metal imbalances are reported to be one of the etiological factors of neurological diseases like Bipolar Disorders (BPD), Alzheimer’s disease (AD) and Parkinson’s disease (PD). Moreover, metals like Aluminium (Al) and iron (Fe) are found to be increased in specific regions of neurodegenerative brain of AD and PD. These two metals play a pivotal role in neurotoxicity and neurodegeneration. They cause neurofibrillary tangles formation (NFTs), amyloid beta and α-synuclein aggregation. Further, Al in conjunction with Fe promotes oxidative stress and apoptosis. Thus Fe, Al plays a significant role in neuronal cell death. DNA dynamics is an essential parameter for normal neuronal cell function. Metal ions interact with DNA, might show significant changes in structure and function. Al and Fe are reported to cause cellular toxicity through their interaction with DNA. DNA damage causes genomic instability and cell death. Moreover nuclear localization of Al and Fe has been observed in AD and PD brain. Recent reports from our lab showed the presence of Z-DNA in hippocampus of AD brain. It was also hypothesized that environmental factors like metals (Al, Fe), oxidative stress, and trace metal homeostasis imbalance might be responsible for the DNA topological changes seen in AD brain. However, there are no studies on Al, Fe in modulating DNA topology and stability and its relevance to neuronal cell death. The present study was focused to understand the Al, Fe interaction with DNA, trace metal homeostasis in serum and brain samples of bipolar disorders, genomic DNA conformation and stability of bipolar depression brain.

Item Type: Thesis (PhD)
Uncontrolled Keywords: neurological diseases Trace elements DNA stability Metal - DNA interaction
Subjects: 600 Technology > 01 Medical sciences > 02 Anatomy
600 Technology > 01 Medical sciences > 17 Toxicology
Divisions: Dept. of Biochemistry
Depositing User: Food Sci. & Technol. Information Services
Date Deposited: 13 Feb 2008 04:50
Last Modified: 28 Dec 2011 09:32
URI: http://ir.cftri.com/id/eprint/1642

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