RT Journal Article
SR Electronic
T1 A novel mitochondrial enriched antioxidant protects neurons against acute oxidative stress
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 109439
DO 10.1101/109439
A1 Nicola J. Drummond
A1 Nick O. Davies
A1 Janet E. Lovett
A1 Mark R. Miller
A1 Graeme Cook
A1 Thomas Becker
A1 Catherina G. Becker
A1 Donald B. McPhail
A1 Tilo Kunath
YR 2017
UL http://biorxiv.org/content/early/2017/02/17/109439.abstract
AB 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 mitochondrial localisation of Proxison. Importantly, in vivo administration of Proxison demonstrated effective and well tolerated neuroprotection against oxidative stress in a zebrafish model of dopaminergic neuronal loss.