Oxidative stress regulates the ubiquitin–proteasome system and immunoproteasome functioning in a mouse model of X-adrenoleukodystrophy

• DOI: 10.1093/brain/aws370
• Publication Date: 2013-02-25T00:38:10Z
• Authors: Nathalie Launay; Montserrat Ruiz; Stéphane Fourcade; Agatha Schlüter; Cristina Guilera; Isidre Ferrer; Erwin Knecht; Aurora Pujol
• Keywords: Adrenoleukodystrophy; Proteostasis; Mitochondrial respiratory chain

Oxidative damage is a pivotal aetiopathogenic factor in X-linked adrenoleukodystrophy. This neurometabolic disease characterized by the accumulation of very-long-chain fatty acids owing to loss function peroxisomal transporter Abcd1. Here, we used adrenoleukodystrophy mouse model and patient's fibroblasts detect malfunctioning ubiquitin–proteasome system resulting from oxidatively modified proteins, some involved bioenergetic metabolism. Furthermore, immunoproteasome machinery appears upregulated response oxidative stress, absence overt inflammation. i-Proteasomes are recruited mitochondria when exposed an excess stress. Antioxidant treatment regulates proteasome expression, prevents i-proteasome induction translocation i-proteasomes mitochondria. Our findings support key role quality control during adrenoleukodystrophy, perhaps other neurodegenerative conditions with similar pathogeneses.