Neuroprotective actions of 2,4-dinitrophenol: Friend or foe?

2,4-dinitrophenol (DNP) has long been known to be toxic at high concentrations, an effect related to uncoupling of mitochondrial oxidative phosphorylation. Five years ago, however, we reported that low concentrations of DNP protect neurons against the toxicity of the amyloid-β peptide. Since then, a number of other studies have provided evidence of beneficial actions of DNP (at low concentrations), including neuroprotection against different types of insult, blockade of amyloid aggregation, stimulation of neurite outgrowth and neuronal differentiation, and even extension of lifespan in certain organisms.