Biomedical subjects

Fatiha Boukhtouche

Publications and source records attributed to Fatiha Boukhtouche.

4 recordsLinked to original sources

PubMed2006

Retinoid-related orphan receptor alpha controls the early steps of Purkinje cell dendritic differentiation.

Dendritic differentiation involves both regressive and growth events. The mechanisms controlling the regressive events are poorly understood. This study is aimed at determining the role of the nuclear receptor retinoid-related orphan receptor alpha (RORalpha) in Purkinje cell (PC) dendritic differentiation in organotypic cultures. As observed in vivo, in these cultures, fusiform PCs with embryonic bipolar shape undergo regression before the outgrowth of the ultimate dendritic tree. We show that lentiviral-mediated hRORalpha1 overexpression in fusiform PCs leads to a cell-autonomous accelerated progression of dendritic differentiation. In addition, RORalpha is necessary for the PC regressive events: whereas staggerer RORalpha-deficient PCs remain in the embryonic fusiform stage, replacement of hRORalpha1 restores normal dendritogenesis. These results demonstrate that RORalpha expression in fusiform PCs is crucial for the dendritic regression and progression of the following step of extension of dendritic processes. However, it does not seem to participate to the last stage of dendritic growth. This study identifies RORalpha as a nuclear receptor crucial for the control of dendritic remodeling during development.

Animals↗

PubMed2006

RORalpha, a pivotal nuclear receptor for Purkinje neuron survival and differentiation: from development to ageing.

RORalpha (Retinoid-related Orphan Receptor) is a transcription factor belonging to the superfamily of nuclear receptors. The spontaneous staggerer (sg) mutation, which consists of a deletion in the Rora gene, has been shown to cause the loss of function of the RORalpha protein. The total loss of RORalpha expression leads to cerebellar developmental defects, particularly to a dramatic decreased survival of Purkinje cells and an early block in the differentiation process. This review focuses on recent studies which position RORalpha as a pivotal factor controlling Purkinje cell survival and differentiation, from development to ageing.

Animals↗

PubMed2006

Human retinoic acid receptor-related orphan receptor alpha1 overexpression protects neurones against oxidative stress-induced apoptosis.

Retinoic acid receptor-related orphan receptor alpha (RORalpha) 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 RORalpha. To test this hypothesis, the survival rate of lentiviral-mediated human RORalpha1-overexpressing neurones has been evaluated in response to different stressors disturbing the redox homeostasis, such as beta-amyloid peptide, c(2)-ceramide and H(2)O(2). We show that overexpression of human RORalpha1 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 RORalpha is predominantly mediated by glutathione peroxidase 1 and peroxiredoxin 6. These results suggest a new role for RORalpha 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.

Aging↗

PubMed2004

The "CholesteROR" protective pathway in the vascular system.

Retinoic acid receptor-related Orphan Receptor alpha (RORalpha) is a member of the nuclear hormone receptor superfamily. RORalpha has long been considered as a constitutive activator of transcription in the absence of exogenous ligand; however, cholesterol has recently been identified as a natural ligand of RORalpha. The spontaneous staggerer (sg/sg) mutation is a deletion in the Rora gene that prevents the translation of the ligand-binding domain (LBD), leading to the loss of RORalpha activity. The homozygous Rora(sg/sg) mutant mouse, of which the most obvious phenotype is ataxia associated with cerebellar degeneration, also displays a variety of other phenotypes, including several vascular ones; in particular, dysfunction of smooth muscle cells and enhanced susceptibility to atherosclerosis. Moreover, RORalpha appears to participate in the regulation of plasma cholesterol levels, and has been shown to positively regulate apolipoprotein (apo)A-I and apoC-III gene expression. Yet its activity is regulated by cholesterol itself, making RORalpha an intracellular cholesterol target.

Animals↗