TY - JOUR T1 - A novel mitochondrial enriched antioxidant protects neurons against acute oxidative stress JF - bioRxiv DO - 10.1101/109439 SP - 109439 AU - Nicola J. Drummond AU - Nick O. Davies AU - Janet E. Lovett AU - Mark R. Miller AU - Graeme Cook AU - Thomas Becker AU - Catherina G. Becker AU - Donald B. McPhail AU - Tilo Kunath Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/02/17/109439.abstract N2 - 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. ER -