Hot off the Press: A potentially new target for stroke recovery… ‘Nox’ at the door

While many sources of ROS contribute to oxidative stress (xanthine oxidases, lipoxygenases and mitochondrial respiratory chain oxidation), Nox enzymes produce physiologically significant O 2 -• and H2O2 throughout the body (reviewed in 4 ).The Nox family consists of seven members (Nox1-5, Duox1-2).Nox5 is potentially a good target for therapies because it differs from other Nox isoforms in terms of its activation and tissue distribution.Most Nox isoforms are dependent on protein cofactors for their activity (e.g., p22phox), but Nox5 is not 5 .Furthermore, while Nox5 is structurally similar to other Noxes in that it contains conserved C-terminal NADPH and FAD binding domains and 6 transmembrane-spanning regions, its amino terminus harbours multiple EF-hands that regulate its activity in response to intracellular Ca 2+ 6 .Phosphorylation of amino acid residues alters EF-hand domain conformation to enhance Nox5 sensitivity to physiological Ca 2+ levels 7 .