Adrenoleukodystrophy: The Restoration of Peroxisomal β-Oxidaton by Transfection of Normal cDNA

Abstract

In order to elucidate the function of ALDP [a protein encoded by the gene responsible for adrenoleukodystrophy (ALD)], normal ALDP cDNA, inserted in an expression vector driven by chicken β-actin promotor, was transfected into ALE fibroblasts. In a transient expression system, the fatty acid composition did not change even though the ALDP was newly synthesized based on the findings of a western blot analysis. In a stable expression system, 3 cell lines were strongly positive for ALDP. In these cells the level of very long chain fatty acid (C26:0) turned out to be as low as those of the control, while the activities of C24 β-oxidation, as checked by two different methods, became normal. From these results, it is concluded that ALDP is indispensable for the function of peroxisomal β-oxidation, and thus the treatment of ALD may be possible by the supplementation of ALDP.