‘Don't be so over-protective!’

» . . .the findings reported by Schäfer et al are the first to link Nrf2 action to the modulation of the skin barrier.« reactive oxygen species (ROS) and leads to damage of cellular components including proteins, DNA and lipids. This damage is thought to be a key mechanism of aging as well as to be involved in the pathogenesis of so diverse diseases as diabetes, schizophrenia, arteriosclerosis and many more (Ghosh et al, 2011; Negre-Salvayre et al, 2010). It is therefore not surprising that the search for strategies to thwart oxidative stress has been at the centre of research efforts since several decades. Anti-oxidants have been tested as nutrient additives or, as far as the skin is concerned, in topical formulations with variable success. Apart from providing exogenous anti-oxidants, boosting the organism’s own anti-oxidant defense has been proposed as a promising way forward. The redox-regulated transcription factor ‘Nuclear factor, erythroid derived 2, like 2’ (Nrf2) is a central switch in the cellular defense against oxidative stress and agonists of Nrf2 are currently tested in clinical trials (Pergola et al, 2011). Under baseline conditions, Nrf2 is retained in the cytoplasm and proteolytically degraded through binding to Keap1. On exposure to electrophils, Nrf2 is released from Keap1 and relocalizes to the nucleus where it promotes transcription of a wide range of cytoprotective enzymes and cellular