Affinage

ABCD1

ATP-binding cassette sub-family D member 1 · UniProt P33897

Round 2 corrected
Length
745 aa
Mass
82.9 kDa
Annotated
2026-04-28
130 papers in source corpus 21 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ABCD1 is a peroxisomal membrane ABC half-transporter that homodimerizes to form a functional transporter importing very long-chain fatty acyl-CoA esters (preferentially saturated C24:0 and C26:0) from the cytosol into the peroxisome for β-oxidation (PMID:18757502, PMID:21145416, PMID:23671276). Cryo-EM structures reveal that C26:0-CoA binds TM5 residue W339 to stimulate ATPase-driven translocation through the transmembrane domains, with a C-terminal coiled-coil domain negatively modulating NBD activity (PMID:36810450). Loss-of-function mutations cause X-linked adrenoleukodystrophy (X-ALD) through VLCFA accumulation that triggers ER stress, mitochondrial dysfunction, NF-κB/AP-1-mediated neuroinflammation, and c-MYC-dependent blood–brain barrier disruption (PMID:8441467, PMID:9256488, PMID:33690217, PMID:18723473, PMID:26377633, PMID:25393703). PEX19 mediates ABCD1 targeting to the peroxisomal membrane (PMID:10704444).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1993 High

    Positional cloning identified the gene mutated in X-linked adrenoleukodystrophy, revealing it encodes a peroxisomal ABC transporter homolog and thereby establishing the molecular basis of ALD.

    Evidence Positional cloning and cDNA sequence analysis from ALD patient DNA

    PMID:8441467

    Open questions at the time
    • No biochemical function or substrate identified at this stage
    • Protein localization inferred from homology, not directly demonstrated
  2. 1994 High

    Direct visualization of ALDP at the peroxisomal membrane confirmed the predicted subcellular localization and showed the protein is absent in ALD patients, linking loss of a peroxisomal transporter to disease.

    Evidence Immunoelectron microscopy and immunofluorescence with monoclonal antibodies in normal and ALD patient fibroblasts

    PMID:8002973 PMID:8004093

    Open questions at the time
    • No transport activity demonstrated
    • Mechanism of peroxisomal targeting unknown
  3. 1997 High

    Abcd1 knockout mice recapitulated VLCFA accumulation with impaired peroxisomal β-oxidation, establishing that ABCD1 is required in vivo for VLCFA catabolism.

    Evidence Gene-targeted knockout mouse with biochemical β-oxidation assays and tissue lipid analysis

    PMID:9256488

    Open questions at the time
    • Whether ABCD1 directly transports VLCFAs or acts indirectly remained unresolved
    • Mouse model lacked overt demyelination
  4. 1999 Medium

    Demonstration that ALDP forms homodimers and heterodimers with ABCD2/ABCD3, and that disease mutations disrupt dimerization, established that the functional transporter is a dimer and that dimerization loss contributes to X-ALD.

    Evidence Yeast two-hybrid and co-immunoprecipitation with wild-type and mutant ALDP constructs

    PMID:10227685 PMID:10551832

    Open questions at the time
    • In vivo stoichiometry of homo- vs. heterodimers not determined
    • No structural information on the dimer interface
  5. 2000 Medium

    Identification of PEX19 as the cytosolic receptor that binds and delivers ABCD1 to the peroxisomal membrane explained how ALDP reaches its site of action.

    Evidence Co-immunoprecipitation and nuclear mislocalization experiment redirecting PEX19-dependent cargoes

    PMID:10704444

    Open questions at the time
    • Mechanism of membrane insertion after PEX19 delivery not resolved
    • Whether PEX19 binding is rate-limiting for ABCD1 biogenesis unknown
  6. 2004 Medium

    In vivo purification from mouse liver showed ABCD1 exists predominantly as homodimers under physiological conditions, resolving ambiguity about the native oligomeric state.

    Evidence Two-step purification and immunoprecipitation of endogenous ABCD1 complex from mouse liver

    PMID:15276650

    Open questions at the time
    • Liver-specific result; whether homodimers predominate in brain was untested
    • Single tissue examined
  7. 2008 High

    Functional reconstitution of human ABCD1 in yeast demonstrated that the homodimer directly transports acyl-CoA esters across the peroxisomal membrane, definitively establishing ABCD1 as a fatty acyl-CoA transporter.

    Evidence Rescue of yeast pxa1/pxa2Δ mutant by human ABCD1 cDNA with tandem-MS quantification of intracellular acyl-CoA esters

    PMID:18757502

    Open questions at the time
    • Substrate specificity for individual VLCFA-CoA species not yet profiled
    • Whether CoA moiety is transported intact or cleaved was debated
  8. 2008 Medium

    ABCD1 silencing in astrocytes revealed that VLCFA accumulation directly activates NF-κB and AP-1 to drive neuroinflammation, providing a mechanistic link between the metabolic defect and inflammatory demyelination in X-ALD.

    Evidence siRNA knockdown of Abcd1/Abcd2 in primary mouse astrocytes with cytokine measurement and monoenoic fatty acid rescue

    PMID:18723473

    Open questions at the time
    • In vivo validation of NF-κB/AP-1 pathway in ALD brain not provided
    • Relative contributions of astrocytes vs. other cell types to inflammation unclear
  9. 2010 High

    Systematic substrate profiling showed ABCD1 preferentially transports saturated VLCFAs (C24:0, C26:0) whereas ABCD2 prefers polyunsaturated species, explaining the non-redundancy of peroxisomal ABC transporters.

    Evidence Yeast complementation with individual human ABCD1 or ABCD2 cDNAs and substrate-specific β-oxidation assays

    PMID:21145416

    Open questions at the time
    • Structural basis for substrate selectivity unknown
    • In vivo validation of specificity in mammalian cells incomplete
  10. 2013 High

    Antibody-blocking experiments in human fibroblasts proved that ABCD1 directly transports C26:0-CoA into peroxisomes and that residual β-oxidation in X-ALD cells depends on ABCD3, establishing the direct transport model and identifying compensatory pathways.

    Evidence ABCD1-specific antibody blocking in control fibroblasts reducing β-oxidation to X-ALD levels; isolated peroxisome assay

    PMID:23671276

    Open questions at the time
    • Whether CoA is hydrolyzed during translocation remained unresolved
    • ABCD3 compensation not shown to be therapeutically sufficient
  11. 2015 Medium

    ABCD1 loss in brain endothelial cells was shown to downregulate c-MYC, reducing tight junction protein CLDN5 and increasing ICAM1-mediated monocyte transmigration, revealing a cell-autonomous mechanism for blood–brain barrier breakdown in cerebral ALD.

    Evidence siRNA knockdown of ABCD1 in human brain microvascular endothelial cells with MYC epistasis and monocyte transmigration assay

    PMID:26377633

    Open questions at the time
    • In vivo BBB disruption mechanism not confirmed in animal model
    • How VLCFA accumulation leads to c-MYC downregulation not defined
  12. 2015 Medium

    ABCD1 deficiency was found to cause mitochondrial dysfunction including reduced ETC activity, TCA cycle impairment, and redox dysregulation, revealing that peroxisomal VLCFA transport failure has direct mitochondrial consequences.

    Evidence siRNA silencing of ABCD1 in oligodendrocytes and astrocytes with enzyme activity assays and SAHA rescue

    PMID:25393703

    Open questions at the time
    • Molecular mechanism linking VLCFA excess to mitochondrial ETC dysfunction not delineated
    • SAHA rescue could act through off-target HDAC inhibition effects
  13. 2021 Medium

    Saturated VLCFAs were identified as the toxic species causing ER stress in ALD cells, while monounsaturated VLCFAs are non-toxic; pharmacological induction of desaturase SCD1 or LXR agonism reduces VLCFA toxicity, connecting saturation state to pathogenic mechanism.

    Evidence Drug screen in zebrafish ALD model, SCD1 manipulation in human fibroblasts, ER stress assays, Abcd1-/y mouse treatment

    PMID:33690217

    Open questions at the time
    • Clinical translatability of SCD1 induction or LXR agonism not established
    • Whether ER stress is the primary driver vs. a secondary consequence is unclear
  14. 2023 High

    Cryo-EM structures of ABCD1 in four conformational states resolved the complete transport cycle: C26:0-CoA binds W339 in TM5 to stimulate ATPase activity, ATP-driven NBD dimerization opens TMDs to the peroxisomal lumen, and a C-terminal coiled-coil negatively regulates ATPase activity.

    Evidence Cryo-EM (six structures in four states), ATPase activity assays, W339 mutagenesis

    PMID:36810450

    Open questions at the time
    • Fate of the CoA moiety during translocation not resolved structurally
    • Structures obtained in detergent micelles; behavior in native peroxisomal membrane may differ
    • Structural basis for disease-causing missense mutations beyond W339 not systematically mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the structural and biochemical basis by which VLCFA accumulation triggers ER stress, mitochondrial dysfunction, and inflammatory signaling; whether the CoA moiety is cleaved during translocation; and what determines the phenotypic variability between cerebral ALD and AMN in patients with similar mutations.
  • No structure of ABCD1 in native peroxisomal membrane
  • Genotype-phenotype modifier genes for cerebral ALD vs. AMN not identified mechanistically
  • Quantitative transport kinetics for individual VLCFA-CoA species not measured in reconstituted system

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0140657 ATP-dependent activity 2
Localization
GO:0005777 peroxisome 3
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-1643685 Disease 4 R-HSA-382551 Transport of small molecules 3
Partners
ABCD2ABCD3PEX19
Complex memberships
ABCD1 homodimer

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 The ALD gene was identified by positional cloning; it encodes a putative peroxisomal membrane protein with significant homology to the ATP-binding cassette (ABC) superfamily of transporters, specifically to the 70-kDa peroxisomal membrane protein involved in peroxisome biogenesis. Positional cloning, cDNA isolation, sequence analysis Nature High 8441467
1994 ALDP (the adrenoleukodystrophy protein encoded by ABCD1) is a 75-80 kDa membrane protein localized to the peroxisomal membrane, as demonstrated by immunofluorescence and immunoelectron microscopy; the protein is absent in ALD patients with disease-causing mutations. Monoclonal antibody generation, Western blotting, immunofluorescence, immunoelectron microscopy Human molecular genetics High 8002973 8004093
1995 Missense mutations in ABCD1 can abolish ALDP protein stability or peroxisomal localization; mutations in the carboxy terminus affect protein stabilization, while mutations in the amino-terminal half can still permit some ALDP expression and peroxisomal targeting. Indirect immunofluorescence of patient fibroblasts correlated with mutation analysis American journal of human genetics Medium 7668254
1996 The carboxy terminus of ALDP is required for protein stabilization; frameshift, nonsense, and carboxy-terminal missense mutations result in complete absence of ALDP protein, while amino-terminal missense mutations allow residual ALDP expression. Western blotting and immunofluorescence in patient fibroblasts correlated with mutation type Journal of inherited metabolic disease Medium 8892025
1997 Knockout of the Abcd1 gene in mice results in reduced peroxisomal beta-oxidation of VLCFAs and significantly elevated saturated VLCFA levels in all tissues, confirming that ABCD1 (not VLCS) is the gene responsible for X-ALD and that it is required for VLCFA beta-oxidation. Gene targeting (knockout mouse), biochemical beta-oxidation assays, lipid analysis, electron microscopy Proceedings of the National Academy of Sciences of the United States of America High 9256488
1999 ALDP forms homodimers with itself and heterodimers with other peroxisomal ABC half-transporters (ALDRP/ABCD2 and PMP70/ABCD3); two X-ALD disease mutations in the carboxy-terminal half disrupt both homo- and heterodimerization, suggesting that loss of ALDP dimerization contributes to X-ALD pathogenesis. Yeast two-hybrid system, co-immunoprecipitation Neurochemical research Medium 10227685
1999 ALDP overexpression by itself restores peroxisomal VLCFA beta-oxidation in SV40T-transformed cells (which have reduced ALDP and impaired VLCFA oxidation), demonstrating that ALDP is a fundamental, rate-limiting component of peroxisomal VLCFA beta-oxidation and may act as a 'gatekeeper' for VLCFA homeostasis. ALDP overexpression in SV40T-transformed fibroblasts, peroxisomal beta-oxidation assay Molecular genetics and metabolism Medium 10068511
1999 ALDP homo- and heterodimerizes with peroxisomal ABC half-transporters ALDRP and PMP70; two ALD disease mutations in the C-terminal half abolish both homo- and heterodimerization as demonstrated by yeast two-hybrid and co-immunoprecipitation. Yeast two-hybrid, co-immunoprecipitation The Journal of biological chemistry Medium 10551832
2001 Deletion of the ABCD1 ATG translation initiation codon results in expression of an N-terminally truncated ALDP (missing first 65 amino acids) via internal translation initiation; this truncated protein is correctly trafficked to peroxisomes but reduces VLCFA beta-oxidation to ~20% of normal and uniformly causes AMN phenotype in the affected family. Genomic sequencing, RT-PCR, Western blotting, immunofluorescence, in vitro VLCFA beta-oxidation assay Neurology Medium 11739809
2003 ALDP facilitates the functional interaction between peroxisomes and mitochondria; in ALD mouse tissues, peroxisomal VLCFA beta-oxidation is normal despite elevated VLCFA levels, suggesting that ALDP's primary role involves coordinating peroxisome-mitochondria cross-talk rather than directly determining beta-oxidation rate, and mitochondrial structural abnormalities were found in adrenal cortical cells of ALD mice. ALD mouse tissue beta-oxidation assays, pharmacological VLCFA reduction, electron microscopy of adrenal cells Molecular and cellular biology Medium 12509471
2004 In vivo, mouse liver ALDP forms predominantly homomeric complexes; no evidence of heteromeric interactions with PMP70 or accessory proteins was found under normal expression conditions, indicating homomers are the predominant functional units. Two-step purification of PMP70 complex, preparative immunoprecipitation of ALDP complex from mouse liver, protein identification Biochimica et biophysica acta Medium 15276650
2008 Human ABCD1 (ALDP) functions as a homodimer and is involved in the transport of acyl-CoA esters across the peroxisomal membrane; expression of human ABCD1 cDNA alone rescued the pxa1/pxa2Δ yeast mutant phenotype, and tandem-MS analysis of intracellular acyl-CoA esters demonstrated that the Pxa1p/Pxa2p heterodimer (and by extension ABCD1 homodimer) transports a spectrum of acyl-CoA esters. Yeast complementation assay, tandem-MS quantification of intracellular acyl-CoA esters FASEB journal High 18757502
2008 Silencing of Abcd1 (ALDP) and Abcd2 (ALDRP) genes in mouse primary astrocytes causes VLCFA accumulation and triggers an inflammatory response mediated by transcription factors NF-κB, AP-1, and C/EBP; correction of the metabolic defect with monoenoic fatty acids reduced inducible nitric oxide synthase and inflammatory cytokine expression, directly linking VLCFA accumulation to inflammation. siRNA-mediated gene silencing in primary astrocytes, cytokine measurement, transcription factor analysis, monoenoic FA rescue experiment Journal of lipid research Medium 18723473
2010 Human ABCD1 and ABCD2 have distinct substrate specificities for peroxisomal fatty acid beta-oxidation transport; ABCD1 preferentially transports saturated very long-chain fatty acids (C24:0, C26:0), while ABCD2 preferentially transports polyunsaturated VLCFAs (C22:6, C24:6) and C22:0, as determined by fatty acid oxidation studies in pxa1/pxa2Δ yeast expressing each human transporter. Yeast complementation assay with individual human ABCD1 or ABCD2 cDNAs, fatty acid beta-oxidation studies with specific substrates Biochimica et biophysica acta High 21145416
2013 The peroxisomal beta-oxidation defect in X-ALD is directly caused by ABCD1 dysfunction: blocking ABCD1 with a specific antibody in control fibroblasts reduced beta-oxidation to X-ALD levels; C26:0-CoA esters are transported by ABCD1 independently of additional CoA synthetase activity, and residual beta-oxidation of C26:0-CoA in X-ALD fibroblasts is mediated by ABCD3. Primary human fibroblast beta-oxidation assays, specific antibody blocking of ABCD1, mRNA/protein quantification, isolated peroxisome assay The Journal of biological chemistry High 23671276
2015 Silencing of ABCD1 in human brain microvascular endothelial cells causes downregulation of the transcription factor c-MYC, which in turn decreases tight junction protein CLDN5 and increases adhesion molecule ICAM1, leading to greater monocyte adhesion and transmigration; MYC silencing alone mimics ABCD1 silencing effects on endothelial barrier function. siRNA silencing of ABCD1 in human brain microvascular endothelial cells, PCR array, MYC silencing epistasis experiment, monocyte transmigration assay Brain : a journal of neurology Medium 26377633
2015 ABCD1 deletion in oligodendrocytes and astrocytes causes mitochondrial structural and functional perturbations including reduced electron transport chain enzyme activities, reduced TCA cycle activity, dysregulated mitochondrial redox status, and disrupted membrane potential; these mitochondrial defects are corrected by the HDAC inhibitor SAHA. siRNA silencing of ABCD1 in B12 oligodendrocytes and U87 astrocytes, enzyme activity assays for ETC and TCA cycle, mitochondrial membrane potential measurement, SAHA rescue Journal of neurochemistry Medium 25393703
2000 PEX19 binds ALDP (ABCD1) and other peroxisomal membrane proteins; PEX19 is predominantly cytoplasmic and is required for peroxisomal membrane protein targeting and insertion, providing the mechanism by which ABCD1 is delivered to the peroxisomal membrane. Co-immunoprecipitation, mislocalization experiment (nuclear PEX19 leads to nuclear accumulation of PMPs), PMP binding assays The Journal of cell biology Medium 10704444
2021 Saturated VLCFAs cause ER stress in ALD fibroblasts whereas monounsaturated VLCFAs do not; pharmacological induction of SCD1 (stearoyl-CoA desaturase-1) shifts VLCFA from saturated to monounsaturated forms, reducing VLCFA toxicity; in Abcd1-/y mice, LXR agonist treatment reduces VLCFA levels in ALD-relevant tissues. Drug screen in zebrafish ALD model, SCD1 pharmacological inhibition/induction in human fibroblasts, CRISPR knockout of scd1 in zebrafish, ER stress assays, Abcd1-/y mouse dietary LXR agonist treatment The Journal of clinical investigation Medium 33690217
2023 Cryo-EM structures of human ABCD1 in four distinct conformational states reveal that: two transmembrane domains form the substrate translocation pathway; two nucleotide-binding domains form the ATP-binding/hydrolysis site; C26:0-CoA binds to the TMDs and stimulates ATPase activity; W339 in TM5 is essential for substrate binding and stimulation of ATP hydrolysis; a unique C-terminal coiled-coil domain negatively modulates NBD ATPase activity; the outward-facing state shows ATP-driven NBD dimerization opening the TMDs to the peroxisomal lumen for substrate release. Cryo-electron microscopy (6 structures in 4 conformational states), ATPase activity assays, mutagenesis of W339 Signal transduction and targeted therapy High 36810450

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
1993 Putative X-linked adrenoleukodystrophy gene shares unexpected homology with ABC transporters. Nature 1003 8441467
2005 The DNA sequence of the human X chromosome. Nature 816 15772651
2006 Biochemistry of mammalian peroxisomes revisited. Annual review of biochemistry 761 16756494
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2012 X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet journal of rare diseases 411 22889154
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2012 Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature 319 22810586
2016 Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics. Cell reports 306 27342126
1981 Adrenoleukodystrophy: evidence for X linkage, inactivation, and selection favoring the mutant allele in heterozygous cells. Proceedings of the National Academy of Sciences of the United States of America 272 6795626
2007 X-linked adrenoleukodystrophy. Nature clinical practice. Neurology 267 17342190
2000 PEX19 binds multiple peroxisomal membrane proteins, is predominantly cytoplasmic, and is required for peroxisome membrane synthesis. The Journal of cell biology 259 10704444
1984 Adrenoleukodystrophy: survey of 303 cases: biochemistry, diagnosis, and therapy. Annals of neurology 253 6524872
2002 Control of germination and lipid mobilization by COMATOSE, the Arabidopsis homologue of human ALDP. The EMBO journal 231 12065405
1994 The gene responsible for adrenoleukodystrophy encodes a peroxisomal membrane protein. Human molecular genetics 229 8004093
1997 A mouse model for X-linked adrenoleukodystrophy. Proceedings of the National Academy of Sciences of the United States of America 228 9256488
2001 ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations. Human mutation 226 11748843
2011 Toward an understanding of the protein interaction network of the human liver. Molecular systems biology 207 21988832
2012 X-linked adrenoleukodystrophy: clinical, metabolic, genetic and pathophysiological aspects. Biochimica et biophysica acta 205 22483867
2016 Adrenoleukodystrophy - neuroendocrine pathogenesis and redefinition of natural history. Nature reviews. Endocrinology 195 27312864
2008 The human peroxisomal ABC half transporter ALDP functions as a homodimer and accepts acyl-CoA esters. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 187 18757502
2014 X-linked adrenoleukodystrophy in women: a cross-sectional cohort study. Brain : a journal of neurology 176 24480483
2010 A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder. Schizophrenia research 172 20889312
2009 Transcriptomic and genetic studies identify IL-33 as a candidate gene for Alzheimer's disease. Molecular psychiatry 170 19204726
2013 Pathophysiology of X-linked adrenoleukodystrophy. Biochimie 165 24316281
1999 X-linked adrenoleukodystrophy: genes, mutations, and phenotypes. Neurochemical research 147 10227685
2006 X-linked adrenoleukodystrophy: clinical, biochemical and pathogenetic aspects. Biochimica et biophysica acta 146 16949688
2019 Mapping the proximity interaction network of the Rho-family GTPases reveals signalling pathways and regulatory mechanisms. Nature cell biology 137 31871319
2017 RNA-binding activity of TRIM25 is mediated by its PRY/SPRY domain and is required for ubiquitination. BMC biology 135 29117863
2020 X-linked adrenoleukodystrophy: Pathology, pathophysiology, diagnostic testing, newborn screening and therapies. International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience 130 31909500
2014 X-linked adrenoleukodystrophy: pathogenesis and treatment. Current neurology and neuroscience reports 123 25115486
1997 X linked adrenoleukodystrophy: clinical presentation, diagnosis, and therapy. Journal of neurology, neurosurgery, and psychiatry 116 9221959
2013 Impaired very long-chain acyl-CoA β-oxidation in human X-linked adrenoleukodystrophy fibroblasts is a direct consequence of ABCD1 transporter dysfunction. The Journal of biological chemistry 115 23671276
2010 Pathomechanisms underlying X-adrenoleukodystrophy: a three-hit hypothesis. Brain pathology (Zurich, Switzerland) 115 20626745
1995 Altered expression of ALDP in X-linked adrenoleukodystrophy. American journal of human genetics 115 7668254
1995 Spectrum of mutations in the gene encoding the adrenoleukodystrophy protein. American journal of human genetics 115 7825602
1999 Homo- and heterodimerization of peroxisomal ATP-binding cassette half-transporters. The Journal of biological chemistry 114 10551832
1997 Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity. Human molecular genetics 112 9215666
2010 General aspects and neuropathology of X-linked adrenoleukodystrophy. Brain pathology (Zurich, Switzerland) 109 20626743
2010 Differential substrate specificities of human ABCD1 and ABCD2 in peroxisomal fatty acid β-oxidation. Biochimica et biophysica acta 109 21145416
2003 Role of ALDP (ABCD1) and mitochondria in X-linked adrenoleukodystrophy. Molecular and cellular biology 108 12509471
1994 X-linked adrenoleukodystrophy (ALD): a novel mutation of the ALD gene in 6 members of a family presenting with 5 different phenotypes. Biochemical and biophysical research communications 106 7811247
2018 Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. Molecular & cellular proteomics : MCP 101 30021884
1999 The neurobiology of X-linked adrenoleukodystrophy, a demyelinating peroxisomal disorder. Trends in neurosciences 97 10088993
2024 Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy. The New England journal of medicine 89 39383458
2010 Biochemical aspects of X-linked adrenoleukodystrophy. Brain pathology (Zurich, Switzerland) 85 20626744
2016 Newborn Screening for X-Linked Adrenoleukodystrophy. International journal of neonatal screening 82 31467997
2015 Brain endothelial dysfunction in cerebral adrenoleukodystrophy. Brain : a journal of neurology 70 26377633
1999 Developmental expression of an amn(+) transgene rescues the mutant memory defect of amnesiac adults. The Journal of neuroscience : the official journal of the Society for Neuroscience 68 10516293
2021 Genetic and epigenetic disease modifiers: non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Translational gastroenterology and hepatology 65 33409397
2015 Oxidative stress, mitochondrial and proteostasis malfunction in adrenoleukodystrophy: A paradigm for axonal degeneration. Free radical biology & medicine 61 26073123
2024 Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy. The New England journal of medicine 58 39383459
1996 Identification of mutations in the ALD-gene of 20 families with adrenoleukodystrophy/adrenomyeloneuropathy. Human genetics 56 8566952
2008 Silencing of Abcd1 and Abcd2 genes sensitizes astrocytes for inflammation: implication for X-adrenoleukodystrophy. Journal of lipid research 55 18723473
2018 Impaired plasticity of macrophages in X-linked adrenoleukodystrophy. Brain : a journal of neurology 53 29860501
2020 The Changing Face of Adrenoleukodystrophy. Endocrine reviews 52 32364223
2008 Interactions of cubilin with megalin and the product of the amnionless gene (AMN): effect on its stability. The Biochemical journal 50 17990981
1995 Tumor necrosis factor-alpha and X-linked adrenoleukodystrophy. Journal of neuroimmunology 50 7593551
2004 Progress in X-linked adrenoleukodystrophy. Current opinion in neurology 48 15167059
2022 Treatment of cerebral adrenoleukodystrophy: allogeneic transplantation and lentiviral gene therapy. Expert opinion on biological therapy 46 36107226
2010 AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2. Traffic (Copenhagen, Denmark) 46 20088845
2005 X-linked adrenoleukodystrophy: therapeutic approaches to distinct phenotypes. Pediatric transplantation 46 16305618
2011 Adrenoleukodystrophy in female heterozygotes: underrecognized and undertreated. Molecular genetics and metabolism 45 22112817
2020 Extracellular Vesicles in NAFLD/ALD: From Pathobiology to Therapy. Cells 44 32231001
2004 Mouse liver PMP70 and ALDP: homomeric interactions prevail in vivo. Biochimica et biophysica acta 42 15276650
2022 Probiotic-derived nanoparticles inhibit ALD through intestinal miR194 suppression and subsequent FXR activation. Hepatology (Baltimore, Md.) 41 35689610
2019 CRISPR/Cas9-mediated knockout of Abcd1 and Abcd2 genes in BV-2 cells: novel microglial models for X-linked Adrenoleukodystrophy. Biochimica et biophysica acta. Molecular and cell biology of lipids 39 30769094
2007 The Arabidopsis ALDP protein homologue COMATOSE is instrumental in peroxisomal acetate metabolism. The Biochemical journal 39 17581114
2006 Therapy of X-linked adrenoleukodystrophy. NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics 39 16554262
1995 Clinical and therapeutic aspects of adrenoleukodystrophy and adrenomyeloneuropathy. Journal of neuropathology and experimental neurology 39 7666063
2011 X-linked adrenoleukodystrophy: ABCD1 de novo mutations and mosaicism. Molecular genetics and metabolism 38 21700483
2016 Endocrine Dysfunction in X-Linked Adrenoleukodystrophy. Endocrinology and metabolism clinics of North America 36 27241966
2012 The inflammatory response in acyl-CoA oxidase 1 deficiency (pseudoneonatal adrenoleukodystrophy). Endocrinology 36 22508517
1997 Mutations in the adrenoleukodystrophy gene. Human mutation 36 9195223
2015 ABCD1 deletion-induced mitochondrial dysfunction is corrected by SAHA: implication for adrenoleukodystrophy. Journal of neurochemistry 35 25393703
2021 Metabolic rerouting via SCD1 induction impacts X-linked adrenoleukodystrophy. The Journal of clinical investigation 33 33690217
2002 Characterization of breakpoint sequences of five rearrangements in L1CAM and ABCD1 (ALD) genes. Human mutation 33 11968085
1996 ALDP expression in fibroblasts of patients with X-linked adrenoleukodystrophy. Journal of inherited metabolic disease 31 8892025
2024 Lipidomic biomarkers in plasma correlate with disease severity in adrenoleukodystrophy. Communications medicine 30 39256476
2022 Sex-specific newborn screening for X-linked adrenoleukodystrophy. Journal of inherited metabolic disease 30 36256460
2012 Preferential expression of mutant ABCD1 allele is common in adrenoleukodystrophy female carriers but unrelated to clinical symptoms. Orphanet journal of rare diseases 29 22280810
2008 Therapy of X-linked adrenoleukodystrophy. Expert review of neurotherapeutics 29 18759549
1998 Clinical and genetic aspects of X-linked adrenoleukodystrophy. Neuropediatrics 29 9553942
2014 Genotype-phenotype correlation of contiguous gene deletions of SLC6A8, BCAP31 and ABCD1. Clinical genetics 28 24597975
2015 An overview of the genetics, mechanisms and management of NAFLD and ALD. Clinical medicine (London, England) 26 26634687
2006 Immunopathogenesis of adrenoleukodystrophy: current understanding. Journal of neuroimmunology 26 17125847
2005 ABCD1 gene mutations in Chinese patients with X-linked adrenoleukodystrophy. Pediatric neurology 25 16087056
2024 Alcohol-related liver disease (ALD): current perspectives on pathogenesis, therapeutic strategies, and animal models. Frontiers in pharmacology 22 39669199
1993 Adrenoleukodystrophy gene: unexpected homology to a protein involved in peroxisome biogenesis. Biochimie 22 8507690
1989 Structure and regulation of the AMP nucleosidase gene (amn) from Escherichia coli. Biochemistry 22 2690948
2023 X-linked adrenoleukodystrophy and primary adrenal insufficiency. Frontiers in endocrinology 21 38034003
2018 Epigenomic signature of adrenoleukodystrophy predicts compromised oligodendrocyte differentiation. Brain pathology (Zurich, Switzerland) 21 29476661
2017 Antioxidant Capacity and Superoxide Dismutase Activity in Adrenoleukodystrophy. JAMA neurology 21 28288261
2011 Luminal expression of cubilin is impaired in Imerslund-Grasbeck syndrome with compound AMN mutations in intron 3 and exon 7. Haematologica 21 21750092
2008 X-linked adrenoleukodystrophy phenotype is independent of ABCD2 genotype. Biochemical and biophysical research communications 21 18834860
2001 ABCD1 translation-initiator mutation demonstrates genotype-phenotype correlation for AMN. Neurology 21 11739809
1995 Adrenoleukodystrophy: molecular genetics, pathology, and Lorenzo's oil. Brain pathology (Zurich, Switzerland) 21 8520725
2018 Profiling and Imaging of Phospholipids in Brains of Abcd1-Deficient Mice. Lipids 20 29469952
2012 Bezafibrate for X-linked adrenoleukodystrophy. PloS one 20 22911730
2023 Newborn screening for adrenoleukodystrophy: International experiences and challenges. Molecular genetics and metabolism 18 37979237
2021 Molecular Biomarkers for Adrenoleukodystrophy: An Unmet Need. Cells 18 34943935
2020 Vorinostat in the acute neuroinflammatory form of X-linked adrenoleukodystrophy. Annals of clinical and translational neurology 18 32359032
2018 Etiology and treatment of adrenoleukodystrophy: new insights from Drosophila. Disease models & mechanisms 18 29739804
2007 [X-linked adrenoleukodystrophy]. Annales d'endocrinologie 18 17532287
1994 Adrenoleukodystrophy gene encodes an 80 kDa membrane protein. Biochemical and biophysical research communications 18 8002973
2023 Emerging targets for therapy in ALD: Lessons from NASH. Hepatology (Baltimore, Md.) 17 36938877
2021 Imaging in X-Linked Adrenoleukodystrophy. Neuropediatrics 17 34192790
2021 Management of adrenoleukodystrophy: From pre-clinical studies to the development of new therapies. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 17 34560537
2021 ABCD1 and X-linked adrenoleukodystrophy: A disease with a markedly variable phenotype showing conserved neurobiology in animal models. Journal of neuroscience research 17 34716609
2020 Neurocognitive benchmarks following transplant for emerging cerebral adrenoleukodystrophy. Neurology 17 32616675
2023 Structural insights into substrate recognition and translocation of human peroxisomal ABC transporter ALDP. Signal transduction and targeted therapy 16 36810450
2010 Adrenoleukodystrophy. Endocrine development 16 21164268
1999 Peroxisomal very long chain fatty acid beta-oxidation activity is determined by the level of adrenodeukodystrophy protein (ALDP) expression. Molecular genetics and metabolism 16 10068511
1986 Familial spinocerebellar degeneration as an expression of adrenoleukodystrophy. Journal of neurology, neurosurgery, and psychiatry 16 3468205
2020 Deciphering the modifiers for phenotypic variability of X-linked adrenoleukodystrophy. World journal of biological chemistry 15 33274015
2001 Characterisation of two mutations in the ABCD1 gene leading to low levels of normal ALDP. Human genetics 15 11810273
1995 Adrenoleukodystrophy. Current opinion in neurology 15 7551122
2024 Leriglitazone halts disease progression in adult patients with early cerebral adrenoleukodystrophy. Brain : a journal of neurology 14 38832897
2002 Molecular characterization of 21 X-ALD Portuguese families: identification of eight novel mutations in the ABCD1 gene. Molecular genetics and metabolism 14 12175782
2022 ABCD1 Gene Mutations: Mechanisms and Management of Adrenomyeloneuropathy. The application of clinical genetics 13 35983253
2021 Biochemical Studies in Fibroblasts to Interpret Variants of Unknown Significance in the ABCD1 Gene. Genes 13 34946879
2017 Therapeutic strategies in adrenoleukodystrophy. Wiener medizinische Wochenschrift (1946) 13 28493141
2009 Early neuropsychological signs of childhood adrenoleukodystrophy (ALD). Brain & development 13 19497692
1987 Adrenoleukodystrophy: biochemical procedures in diagnosis, prevention and treatment. Journal of inherited metabolic disease 13 3119941