Afficher la couverture 'Alteration of the Bcl-x/Bax Ratio in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis: Evidence for the Implication of the p53 Signaling Pathway | Gonzalez de Aguilar, Jose-Luis' en grand format
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Alteration of the Bcl-x/Bax Ratio in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis: Evidence for the Implication of the p53 Signaling Pathway

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Gonzalez de Aguilar, Jose-Luis | Gordon, Jon | Rene, Frédérique | de Tapia, Marc | Lutz-Bucher, Bernadette | Gaiddon, Christian | Loeffler, Jean-Philippe

Edité par CCSD ; Elsevier -

International audience. Molecular mechanisms promoting neuronal death in amyotrophic lateral sclerosis (ALS) were investigated using transgenic mice that overexpressed the G86R mutated form of the Cu/Zn superoxide dismutase (SOD1) gene. We observed: (i) alteration of the Bcl-x/Bax ratio and (ii) activation of the transcription factor p53, as deduced from its location within neuron nuclei. We further demonstrated that ectopic expression of the G86R mutant SOD1 in PC12 cells enhanced both p53 expression and phosphorylation, leading to transcriptional stimulation of p53-responsive genes. These findings provide evidence that the p53 signaling pathway is activated in SOD1-linked familial ALS and may play a causative role in spinal cord neuron apoptosis by modulating the Bcl-x/Bax ratio.

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