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Human retinoic acid receptor‐related orphan receptor α1 overexpression protects neurones against oxidative stress‐induced apoptosis
Author(s) -
Boukhtouche Fatiha,
Vodjdani Guilan,
Jarvis Christopher I.,
Bakouche Joelle,
Staels Bart,
Mallet Jacques,
Mariani Jean,
LemaigreDubreuil Yolande,
Brugg Bernard
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03708.x
Subject(s) - oxidative stress , retinoic acid , apoptosis , retinoic acid receptor , receptor , orphan receptor , microbiology and biotechnology , chemistry , retinoic acid receptor beta , retinoic acid receptor alpha , retinoic acid receptor gamma , biology , endocrinology , medicine , pharmacology , biochemistry , gene , transcription factor
Abstract 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.