PUBLICATION
A synthetic cell permeable antioxidant protects neurons against acute oxidative stress
- Authors
- Drummond, N.J., Davies, N.O., Lovett, J.E., Miller, M.R., Cook, G., Becker, T., Becker, C.G., McPhail, D.B., Kunath, T.
- ID
- ZDB-PUB-170921-7
- Date
- 2017
- Source
- Scientific Reports 7: 11857 (Journal)
- Registered Authors
- Becker, Catherina G., Becker, Thomas, Davies, Nick O.
- Keywords
- Drug discovery and development, Mechanisms of disease
- MeSH Terms
-
- Flavonoids*/chemistry
- Flavonoids*/pharmacokinetics
- Flavonoids*/pharmacology
- Neurons/metabolism*
- Neurons/pathology
- Cell Line, Tumor
- Oxidative Stress/drug effects*
- Humans
- Free Radical Scavengers*/chemistry
- Free Radical Scavengers*/pharmacokinetics
- Free Radical Scavengers*/pharmacology
- Reactive Oxygen Species/metabolism*
- PubMed
- 28928373 Full text @ Sci. Rep.
Citation
Drummond, N.J., Davies, N.O., Lovett, J.E., Miller, M.R., Cook, G., Becker, T., Becker, C.G., McPhail, D.B., Kunath, T. (2017) A synthetic cell permeable antioxidant protects neurons against acute oxidative stress. Scientific Reports. 7:11857.
Abstract
Excessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinson's disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches. We show that, while it has radical scavenging ability on par with other flavonoids in a cell-free system, Proxison is orders of magnitude more potent than natural flavonoids at protecting neural cells against oxidative stress and is capable of rescuing damaged cells. The unique combination of a lipophilic hydrocarbon tail with a modified polyphenolic head group promotes efficient cellular uptake and moderate mitochondrial enrichment of Proxison. Importantly, in vivo administration of Proxison demonstrated effective and well tolerated neuroprotection against cell loss in a zebrafish model of dopaminergic neurodegeneration.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping