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

Workman, David, Tsatsanis, Andrew, Lewis, Frank, Boyle, John, Mousadoust, Maryam, Hettiarachchi, Nishani, Hunter, Michael, Peers, Chris, Tetard, David and Duce, James (2015) Protection from neurodegeneration in the 6-hydroxydopamine (6-OHDA) model of Parkinson's with novel 1-hydroxypyridin-2-one metal chelators. Metallomics : Integrated Biometal Science, 7 (5). pp. 867-876. ISSN 1756-591X

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Official URL: http://dx.doi.org/10.1039/C4MT00326H

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 and 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 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.

Item Type: Article
Subjects: A300 Clinical Medicine
C700 Molecular Biology, Biophysics and Biochemistry
F100 Chemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Nicola King
Date Deposited: 23 Mar 2015 15:08
Last Modified: 01 Nov 2017 19:51
URI: http://nrl.northumbria.ac.uk/id/eprint/21736

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