X-linked adrenoleukodystrophy: very long-chain fatty acid metabolism, ABC half-transporters and the complicated route to treatment
Abstract
X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene that encodes a peroxisomal membrane located ABC half-transporter named ALDP. Mutations in ALDP result in elevated levels of very long-chain fatty acids (VLCFA) and reduced VLCFA beta-oxidation in peroxisomes. The peroxisomal membrane harbors three additional closely related ABC half-transporters, ALDRP, PMP70 and PMP69 (PMP70R). ABC half-transporters must dimerize to form a functional full-transporter. Whether ALDP forms a homodimer or a heterodimer has not yet been resolved, but most indirect evidence favors homodimerization. The peroxisomal ABC half-transporters are functionally related. Over-expression of ALDRP can correct the biochemical defect both in X-ALD patients cells and the Abcd1 knockout mouse, providing an exciting new possibility for treatment of X-ALD patients. This paper provides an overview of current knowledge and the problems that have been encountered.
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ALDP imports activated very long chain fatty acid acyl-CoA derivatives into peroxisomes where they are shortened by β-oxidation.
“ALDP imports activated very long chain fatty acid acyl-CoA derivatives into peroxisomes where they are shortened by -oxidation (33, 34).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [34]
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- Authors
- Kemp, S., & Wanders, R. J. A.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- Corresponding author
- Kemp, Stephan
- Venue
- Molecular Genetics and Metabolism
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 90
- Issue
- 3
- Pages
- 268-276
- ISSN
- 1096-7192 (ISSN-L)
- OpenAlex
- W2116753947
- Cited by
- 82
- References
- 64
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 5 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 1 · 2017: 2 · 2015: 7 · 2014: 2 · 2013: 1 · 2012: 5
- FWCI
- 4.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Genetics and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Keywords
- X-linked adrenoleukodystrophy, ABCD1 gene, ALDP, very long chain fatty acids, peroxisomal beta-oxidation, PMP70, homodimerization, gene therapy, peroxisomes
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily D, ATP Binding Cassette Transporter, Subfamily D, Member 1, Adrenoleukodystrophy, Animals, Fatty Acids, Humans, Mutation, Phenylbutyrates, Mice, Knockout, ATP-Binding Cassette Transporters, Dimerization, Peroxisomes, Mice
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