| First Author | Fourcade S | Year | 2010 |
| Journal | Hum Mol Genet | Volume | 19 |
| Issue | 10 | Pages | 2005-14 |
| PubMed ID | 20179078 | Mgi Jnum | J:159337 |
| Mgi Id | MGI:4442310 | Doi | 10.1093/hmg/ddq082 |
| Citation | Fourcade S, et al. (2010) Valproic acid induces antioxidant effects in X-linked adrenoleukodystrophy. Hum Mol Genet 19(10):2005-14 |
| abstractText | X-linked adrenoleukodystrophy (X-ALD) is a fatal, axonal demyelinating, neurometabolic disease. It results from the functional loss of a member of the peroxisomal ATP-binding cassette transporter subfamily D (ABCD1), which is involved in the metabolism of very long-chain fatty acids (VLCFA). Oxidative damage of proteins caused by excess of the hexacosanoic acid, the most prevalent VLCFA accumulating in X-ALD, is an early event in the neurodegenerative cascade. We demonstrate here that valproic acid (VPA), a widely used anti-epileptic drug with histone deacetylase inhibitor properties, induced the expression of the functionally overlapping ABCD2 peroxisomal transporter. VPA corrected the oxidative damage and decreased the levels of monounsaturated VLCFA (C26:1 n-9), but not saturated VLCFA. Overexpression of ABCD2 alone prevented oxidative lesions to proteins in a mouse model of X-ALD. A 6-month pilot trial of VPA in X-ALD patients resulted in reversion of the oxidative damage of proteins in peripheral blood mononuclear cells. Thus, we propose VPA as a promising novel therapeutic approach that warrants further clinical investigation in X-ALD. |
