Human retinoic acid receptor‐related orphan receptor α1 overexpression protects neurones against oxidative stress‐induced apoptosis

Retinoic acid receptor‐related orphan receptor α (RORα) is a transcription factor belonging to the superfamily of nuclear receptors. Disruption of the Rora gene in the mouse results in a defect in the development of Purkinje cells leading to a cerebellar atrophy, which suggests a neuroprotective role for RORα. To test this hypothesis, the survival rate of lentiviral‐mediated human RORα1‐overexpressing neurones has been evaluated in response to different stressors disturbing the redox homeostasis , such as β‐amyloid peptide, c 2 ‐ceramide and H 2 O 2 . We show that overexpression of human RORα1 provides neuroprotection by increasing the expression of the antioxidant proteins glutathione peroxidase 1 and peroxiredoxin 6, leading to a reduction in the accumulation of stress‐induced reactive oxygen species. We further demonstrate that the neuroprotective effect of RORα is predominantly mediated by glutathione peroxidase 1 and peroxiredoxin 6. These results suggest a new role for RORα in the control of the neuronal oxidative stress and thus represents a new transcription factor of interest in the regulation of reactive oxygen species‐induced neurodegenerative processes during ageing.