Fibrate induction of the adrenoleukodystrophy‐related gene (ABCD2)

• DOI: 10.1046/j.1432-1327.2001.02249.x
• Publication Date: 2003-03-11T18:11:23Z
• Authors: Stéphane Fourcade; Stéphane Savary; Sabrina Albet; Delphine Gauthé; Catherine Gondcaille; Thierry Pineau; Jérome Bellenger; Marc Bentejac; Andreas Holzinger; Johannes Berger; Maurice Bugaut
• Keywords: Adrenoleukodystrophy; Fibrate; Peroxisomal disorder

X‐linked adrenoleukodystrophy (X‐ALD) is a neurodegenerative disease due to defect in the ABCD1 ( ALD ) gene. , and two close homologues ABCD2 ALDR ABCD3 PMP70 ), are genes encoding ATP‐binding cassette half‐transporters of peroxisomal membrane. As overexpression or gene can reverse biochemical phenotype X‐ALD (reduced β‐oxidation very‐long‐chain fatty acids), pharmacological induction these partially redundant may represent therapeutic approach X‐ALD. We previously reported that could be strongly induced by fibrates, which hypolipidaemic drugs peroxisome‐proliferators rodents. provide evidence dependent on peroxisome proliferator‐activated receptor (PPARα) as both were not fenofibrate‐treated PPARα –/– knock‐out mice. To further characterize pathway, we cloned analysed promoter gene, closest homologue The proximal region (2 kb) rat displayed high conservation with human mouse cognate sequences suggesting an important role regulation Classically, fibrate‐induction involves interaction response element (PPRE) characterized direct repeat AGGTCA‐like motif. Putative PPRE motifs studied isolated form their context gel‐shift assay transfection COS‐7 cells. failed functional PPRE, different mechanism for PPARα‐dependent