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

Doriane Trompier1, Catherine Gondcaille1, Gérard Lizard1

  • 1Laboratoire Bio-PeroxIL, EA7270 University of Bourgogne, 6 Bd Gabriel, Dijon F-21000, France.

Biochemical and Biophysical Research Communications
|February 1, 2014
PubMed

Insights

Targeting ABCD2 gene expression offers a potential therapy for X-linked adrenoleukodystrophy. Upregulating ABCD2 can compensate for ABCD1 gene mutations, restoring fatty acid metabolism and offering hope for neurodegenerative disease treatment.

Area of Science:

  • Biochemistry
  • Genetics
  • Neuroscience

Background:

  • X-linked adrenoleukodystrophy (X-ALD) is a rare neurodegenerative disorder caused by ABCD1 gene mutations.
  • ABCD2 gene expression can compensate for ABCD1 deficiency, restoring peroxisomal very-long-chain fatty acid (VLCFA) metabolism.
  • Identifying therapeutic targets for X-ALD is crucial for disease management.

Purpose of the Study:

  • To review known and novel inducers of ABCD2 gene expression.
  • To explore the therapeutic potential of ABCD2 gene regulation for X-ALD.
  • To discuss the role of LXR antagonists and 22S-hydroxycholesterol as ABCD2 inducers.

Main Methods:

  • Literature review of studies on ABCD2 gene regulation.
  • Analysis of compounds known to induce ABCD2 expression.
  • Examination of recently identified ABCD2 inducers, including LXR antagonists and 22S-hydroxycholesterol.

Main Results:

  • ABCD2 gene up-regulation can restore peroxisomal β-oxidation of VLCFAs in ABCD1 deficiency.
  • Established ABCD2 inducers include phenylbutyrate, HDAC inhibitors, fibrates, DHEA, and thyroid hormone/thyromimetics.
  • LXR antagonists and 22S-hydroxycholesterol are identified as novel inducers of ABCD2 expression.

Conclusions:

  • ABCD2 gene regulation is a promising therapeutic strategy for X-linked adrenoleukodystrophy.
  • LXR antagonists and 22S-hydroxycholesterol represent potential new therapeutic agents for neurodegenerative disorders.
  • Further research into LXR antagonists may yield effective treatments for X-ALD.
Keywords:
ABC transportersAdrenoleukodystrophyLXR antagonistsNeurodegenerative disordersOxysterolsPeroxisome

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