Academic Field

Biological Sciences

Faculty Mentor Name

Dr. Daniel J. Kosman, SUNY Distinguished Professor

Presentation Type

Poster Presentation

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.

Keywords

X-Adrenoleukodystrophy (X-ALD), ATP-binding cassette sub-family D member 1 (ABCD1), Adrenoleukodystrophy protein (ALDP), Very long chain fatty acids (VLCFAs), Oxidative stress, Iron-sulfur clusters, Iron metabolism

Start Date

10-4-2015 2:00 PM

End Date

10-4-2015 2:45 PM

Location

SERC House of Fields

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Apr 10th, 2:00 PM Apr 10th, 2:45 PM

Dysregulation of Iron Metabolism in X-Adrenoleukodystrophy

SERC House of Fields

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.