Moore, S. A. and Huckerby, T. N. and Gibson, G. L. and Fullwood, Nigel J. and Turnbull, Iain and Tabner, Brian J. and El-Agnaf, Omar M. A. and Allsop, David (2004) Both the D-(+) and L-(-) enantiomers of nicotine inhibit Aβ aggregation and cytotoxicity. Biochemistry, 43 (3). pp. 819-826. ISSN 0006-2960Full text not available from this repository.
The underlying cause of Alzheimer's disease is thought to be the aggregation of monomeric -amyloid (A), through a series of toxic oligomers, which forms the mature amyloid fibrils that accumulate at the center of senile plaques. It has been reported that L-(-)-nicotine prevents A aggregation and toxicity, and inhibits senile plaque formation. Previous NMR studies have suggested that this could be due to the specific binding of L-(-)-nicotine to histidine residues (His6, His13, and His14) in the peptide. Here, we have looked at the effects of both of the L-(-) and D-(+) optical enantiomers of nicotine on the aggregation and cytotoxicity of A(1-40). Surprisingly, both enantiomers inhibited aggregation of the peptide and reduced the toxic effects of the peptide on cells. In NMR studies with A(1-40), both enantiomers of nicotine were seen to interact with the three histidine residues. Overall, our data indicate that nicotine can delay A fibril formation and maintain a population of less toxic A species. This effect cannot be due to a highly specific binding interaction between nicotine and A, as previously thought, but could be due instead to weaker, relatively nonspecific binding, or to the antioxidant or metal chelating properties of nicotine. D-(+)-Nicotine, being biologically much less active than L-(-)-nicotine, might be a useful therapeutic agent.
|Journal or Publication Title:||Biochemistry|
|Subjects:||Q Science > QH Natural history > QH301 Biology|
|Departments:||Faculty of Health and Medicine > Biomedical & Life Sciences|
Faculty of Science and Technology > Lancaster Environment Centre
|Deposited By:||Prof David Allsop|
|Deposited On:||15 May 2008 11:46|
|Last Modified:||09 Apr 2014 22:14|
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