Regulation of the adrenoleukodystrophy-related gene (ABCD2): focus on oxysterols and LXR antagonists

Biochem Biophys Res Commun. 2014 Apr 11;446(3):651-5. doi: 10.1016/j.bbrc.2014.01.025. Epub 2014 Jan 27.

Abstract

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.

Keywords: ABC transporters; Adrenoleukodystrophy; LXR antagonists; Neurodegenerative disorders; Oxysterols; Peroxisome.

Publication types

  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D
  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism
  • Adrenoleukodystrophy / drug therapy
  • Adrenoleukodystrophy / genetics*
  • Gene Expression Regulation / drug effects*
  • Humans
  • Hydroxycholesterols / metabolism
  • Hydroxycholesterols / pharmacology
  • Liver X Receptors
  • Molecular Targeted Therapy / methods
  • Orphan Nuclear Receptors / antagonists & inhibitors*
  • Orphan Nuclear Receptors / genetics

Substances

  • ABCD2 protein, human
  • ATP Binding Cassette Transporter, Subfamily D
  • ATP-Binding Cassette Transporters
  • Hydroxycholesterols
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • 22-hydroxycholesterol