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Issue 5, 2015
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Protection from neurodegeneration in the 6-hydroxydopamine (6-OHDA) model of Parkinson's with novel 1-hydroxypyridin-2-one metal chelators

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Abstract

Brain iron accumulation has been associated with inciting the generation of oxidative stress in a host of chronic neurological diseases, including Parkinson's disease. Using the catecholaminergic neurotoxin 6-hydroxydopamine to lesion cellular dopaminergic pathways as a model of Parkinson's disease in culture, a selection of 1-hydroxypyridin-2-one (1,2-HOPO) metal chelators were synthesized and their neuroprotective properties were compared to the 3-hydroxypyridin-4-one; deferiprone (3,4-HOPO; DFP). Protection against 6-OHDA and iron insult by the novel compounds 6 and 9 was comparable to DFP. Iron associated changes by 6-OHDA imply that the neuroprotective capacity of these compounds are due to chelation of the neuronal labile iron pool and the requirement of the iron binding moiety of compound 6 for efficacy supported this hypothesis. In conclusion, two novel 1,2-HOPO's and DFP have comparable neuroprotection against Parkinsonian-associated neurotoxins and supports the continued development of hydroxypyridinone compounds as a non-toxic therapeutic agent in the treatment of neurodegenerative disease.

Graphical abstract: Protection from neurodegeneration in the 6-hydroxydopamine (6-OHDA) model of Parkinson's with novel 1-hydroxypyridin-2-one metal chelators

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Publication details

The article was received on 09 Dec 2014, accepted on 09 Mar 2015 and first published on 10 Mar 2015


Article type: Paper
DOI: 10.1039/C4MT00326H
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Metallomics, 2015,7, 867-876
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    Protection from neurodegeneration in the 6-hydroxydopamine (6-OHDA) model of Parkinson's with novel 1-hydroxypyridin-2-one metal chelators

    D. G. Workman, A. Tsatsanis, F. W. Lewis, J. P. Boyle, M. Mousadoust, N. T. Hettiarachchi, M. Hunter, C. S. Peers, D. Tétard and J. A. Duce, Metallomics, 2015, 7, 867
    DOI: 10.1039/C4MT00326H

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