Abstract
X-Adrenoleukodystrophy (X-ALD), a rare neurodegenerative disease, is an
intricate peroxisomal disorder caused by the inactivation of the ABCD1 gene. As
a result, the encoded protein ALDP, an ATP-binding cassette (ABC) transporter
located in the peroxisomal membrane, impairs the peroxisomal beta-oxidation of
very long chain fatty acids (VLCFAs). This allows further elongation of VLCFAs
resulting in the hyperaccumulation of VLCFAs in plasma and tissues. Oxidative
stress due to excess VLCFAs appears early in the neurodegenerative cascade of
X-ALD. It has been hypothesized that the oxidative stress induced by VLCFAs is
associated with the disruption of iron-sulfur clusters. Iron-sulfur clusters are
indicators of cellular iron status. Thus, we predicted human fibroblast cells with
the ABCD1 gene defect would differentially express genes encoding proteins
involved in iron import and export in comparison to control fibroblasts. Based on
our transcriptional and post-transcriptional in-vitro studies on the relative mRNA
and protein expression related to iron metabolic functions, we have characterized
distinct differences in iron metabolism of patients with X-ALD.
