Regulation of the adrenoleukodystrophy-related gene (ABCD2): focus on oxysterols and LXR antagonists.
The regulation of the ABCD2 gene is recognized as a possible therapeutic target for X-linked adrenoleukodystrophy, a rare neurodegenerative disease caused by mutations in the ABCD1 gene. Up-regulation of ABCD2 expression has indeed been demonstrated to compensate for ABCD1 deficiency, restoring peroxisomal β-oxidation of very-long-chain fatty acids. Besides the known inducers of the ABCD2 gene (phenylbutyrate and histone deacetylase inhibitors, fibrates, dehydroepiandrosterone, thyroid hormone and thyromimetics), this review will focus on LXR antagonists and 22S-hydroxycholesterol, recently described as inducers of ABCD2 expression. Several LXR antagonists have been identified and their possible indication for neurodegenerative disorders will be discussed.
Laboratoire Bio-PeroxIL, EA7270 University of Bourgogne, 6 Bd Gabriel, Dijon F-21000, France.
Doriane
D
Trompier
Laboratoire Bio-PeroxIL, EA7270 University of Bourgogne, 6 Bd Gabriel, Dijon F-21000, France.
Catherine
C
Gondcaille
Laboratoire Bio-PeroxIL, EA7270 University of Bourgogne, 6 Bd Gabriel, Dijon F-21000, France.
Gérard
G
Lizard
Laboratoire Bio-PeroxIL, EA7270 University of Bourgogne, 6 Bd Gabriel, Dijon F-21000, France. Electronic address: stsavary@u-bourgogne.fr.
Stéphane
S
Savary
D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000326:Adrenoleukodystrophy / Q000188:drug therapy / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism / Q000494:pharmacology; D000071518:Liver X Receptors; D058990:Molecular Targeted Therapy / Q000379:methods; D057093:Orphan Nuclear Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics
C431694:ABCD2 protein, human; D000074061:ATP Binding Cassette Transporter, Subfamily D; D018528:ATP-Binding Cassette Transporters; D006888:Hydroxycholesterols; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; C003585:22-hydroxycholesterol
ABC transporters; Adrenoleukodystrophy; LXR antagonists; Neurodegenerative disorders; Oxysterols; Peroxisome