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

David Workman, Andrew Tsatsanis, Frank Lewis, John Boyle, Maryam Mousadoust, Nishani Hettiarachchi, Michael Hunter, Chris Peers, David Tetard, James Duce

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)
18 Downloads (Pure)

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.
Original languageEnglish
Pages (from-to)867-876
JournalMetallomics : Integrated Biometal Science
Volume7
Issue number5
DOIs
Publication statusPublished - 13 May 2015

Fingerprint Dive into the research topics of 'Protection from neurodegeneration in the 6-hydroxydopamine (6-OHDA) model of Parkinson's with novel 1-hydroxypyridin-2-one metal chelators'. Together they form a unique fingerprint.

Cite this