Affinage

ABCD1

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

Length
745 aa
Mass
82.9 kDa
Annotated
2026-06-09
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ABCD1 encodes ALDP, a peroxisomal membrane half-transporter of the ATP-binding cassette superfamily that imports CoA-activated very long-chain fatty acids into the peroxisome for β-oxidation, acting as the rate-limiting gatekeeper of VLCFA homeostasis (PMID:8507690, PMID:8004093, PMID:10068511). ALDP binds and hydrolyzes ATP in a Mg2+-dependent manner (PMID:12176987), and cryo-EM across multiple conformational states shows that C26:0-CoA binds the transmembrane domains—where W339 in TM5 is essential—stimulates NBD ATPase activity, and that ATP-driven NBD dimerization opens the substrate pathway to the peroxisomal lumen for release, with a unique C-terminal coiled-coil domain negatively modulating ATPase activity (PMID:36810450). The functional unit is predominantly an ALDP homodimer, with the C-terminal ~87 residues being the principal interaction domain and also essential for protein stability, such that C-terminal missense and truncating mutations trigger rapid proteasomal degradation, including dominant-negative co-degradation of co-expressed wild-type protein (PMID:8892025, PMID:17609205, PMID:17542813). ALDP function partially overlaps with the related transporter ABCD2 (ALDRP), which physically interacts with ALDP and, when overexpressed, restores peroxisomal β-oxidation and prevents both VLCFA accumulation and neurodegeneration in vivo, while combined ABCD1/ABCD2 loss produces synthetic severity (PMID:9809549, PMID:10196381, PMID:15489218, PMID:21209459, PMID:30769094). ALDP deficiency causes VLCFA accumulation driving downstream pathology: saturated VLCFA-induced ER stress relievable by SCD1-mediated desaturation (PMID:33690217), mitochondrial dysfunction (PMID:25393703), inflammatory activation via NF-κB/AP-1/C/EBP (PMID:18723473), altered cholesterol ester homeostasis (PMID:37759733), and endothelial barrier disruption through c-MYC downregulation (PMID:26377633).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1993 Medium

    Established the molecular identity of the disease gene, predicting that the unknown X-ALD defect lay in a peroxisomal ABC-family transporter rather than directly in fatty acid metabolism.

    Evidence Positional cloning with sequence homology to PMP70 and the ABC superfamily

    PMID:8507690

    Open questions at the time
    • No direct demonstration of transport activity
    • Substrate not biochemically defined
    • Localization inferred from homology only
  2. 1994 High

    Confirmed ALDP is a bona fide peroxisomal membrane protein absent in patients, directly tying the gene product to the peroxisome and to disease.

    Evidence Monoclonal antibody Western blot, immunofluorescence and immunoelectron microscopy in patient and control cells

    PMID:8004093

    Open questions at the time
    • Transport function not shown
    • Membrane topology not resolved
    • No substrate identified
  3. 1995 Medium

    Showed that disease mutations frequently abolish ALDP protein, implicating protein destabilization (not just catalytic loss) as a disease mechanism and assigning a stabilizing role to the C-terminus.

    Evidence Indirect immunofluorescence and mutation analysis across many patient fibroblast lines

    PMID:7668254 PMID:8651290 PMID:8892025

    Open questions at the time
    • No genotype-phenotype correlation found
    • Degradation pathway not defined
    • Mechanism of C-terminal stabilization unknown
  4. 1999 Medium

    Defined ALDP abundance as the rate-limiting determinant of peroxisomal VLCFA β-oxidation, establishing its gatekeeper role.

    Evidence ALDP overexpression rescue of β-oxidation in transformed cells with co-reduced ACOX and ALDP

    PMID:10068511

    Open questions at the time
    • Direct transport mechanism not measured
    • Does not distinguish import of substrate vs. enzyme anchoring
  5. 1999 High

    Demonstrated functional redundancy with the paralog ABCD2 and established that ALDP can self-associate, framing the peroxisomal ABC transporters as overlapping VLCFA handlers.

    Evidence ALDRP cDNA complementation and overexpression in patient fibroblasts with β-oxidation/VLCFA readouts; dimerization and VLCS activity assays; fenofibrate treatment of knockout mice

    PMID:10196381 PMID:10227685 PMID:9809549

    Open questions at the time
    • In vivo predominant oligomeric state unresolved
    • Endogenous vs. forced-expression compensation not separated
    • Heterodimer significance unclear
  6. 2002 High

    Provided direct biochemical proof that ALDP binds and hydrolyzes ATP, confirming it as an active transporter rather than a passive anchor.

    Evidence Photoaffinity labeling with azido-ATP analogs and in vitro ATPase assays on native rat liver peroxisomes

    PMID:12176987

    Open questions at the time
    • Substrate not coupled to ATPase in this study
    • Tyrosine phosphorylation function unknown
    • No vanadate trapping observed
  7. 2004 High

    Resolved the predominant in vivo oligomeric state as homomeric and validated ABCD1–ABCD2 redundancy genetically in whole animals.

    Evidence Native complex purification from mouse liver peroxisomes; transgenic ALDRP overexpression and ABCD1/ABCD2 double-knockout mouse phenotyping

    PMID:15276650 PMID:15489218

    Open questions at the time
    • Native purification contradicts some in vitro heterodimer data
    • Tissue-specific oligomer composition not mapped
  8. 2007 High

    Mapped the dimerization interface to the C-terminus and linked C-terminal mutations to proteasomal, dominant-negative degradation, unifying protein-stability and oligomerization findings.

    Evidence Live-cell FRET with C-terminal deletion constructs, yeast two-hybrid; proteasome-inhibitor rescue of mutant ALDP and co-degradation assays

    PMID:17542813 PMID:17609205

    Open questions at the time
    • Atomic structure of interface not resolved
    • Targeting signal between TM2-TM3 not precisely defined
  9. 2011 High

    Demonstrated a direct ALDP–ALDRP physical interaction with functional consequence, showing the paralogs are not merely redundant but can interact and that ABCD2 has distinct substrate preferences (DHA).

    Evidence Proximity ligation assay, co-IP, and dominant-negative inactive ALDRP-EGFP with substrate-specific β-oxidation assays

    PMID:21209459

    Open questions at the time
    • Stoichiometry of heterocomplex unknown
    • Physiological role of heterodimer vs. homodimer unclear
  10. 2015 Medium

    Connected ALDP loss to cell-type-specific downstream pathology—endothelial barrier breakdown via c-MYC and mitochondrial dysfunction—extending the role beyond VLCFA transport.

    Evidence siRNA silencing in brain microvascular endothelial cells with MYC-knockdown epistasis; siRNA knockdown in oligodendrocyte/astrocyte lines with ETC/TCA enzyme and membrane-potential assays plus SAHA rescue

    PMID:25393703 PMID:26377633

    Open questions at the time
    • Mechanistic link between VLCFA and c-MYC undefined
    • siRNA single-lab in vitro
    • Endothelial effect reported before VLCFA accumulation, mechanism unclear
  11. 2019 High

    Showed in microglia that single ABCD1 loss is buffered by ABCD2, refining the redundancy model to a cell-type-dependent threshold for VLCFA pathology.

    Evidence CRISPR/Cas9 single and double Abcd1/Abcd2 knockout in BV-2 microglia with VLCFA, lipid-inclusion, cholesterol and gene-expression readouts

    PMID:30769094

    Open questions at the time
    • Mechanism of Trem2 dysregulation unresolved
    • Relevance to in vivo microglial disease not established
  12. 2021 High

    Identified saturated VLCFA species as the proximate cause of ER stress and validated SCD1-mediated desaturation as a corrective node, providing a mechanistic basis for lipotoxicity.

    Evidence Zebrafish drug screen and scd1 CRISPR knockout; LXR agonist treatment of Abcd1-/y mice; ER-stress assays in patient fibroblasts

    PMID:33690217

    Open questions at the time
    • Molecular trigger linking VLCFA to UPR not defined
    • Therapeutic translation untested
  13. 2023 High

    Delivered the structural mechanism of substrate transport and uncovered altered cholesterol ester homeostasis as a downstream consequence, defining the transport cycle at near-atomic resolution.

    Evidence Cryo-EM in six conformational states with C26:0-CoA, W339 mutagenesis and substrate-stimulated ATPase assays; lipidomics, gene expression and lipid-droplet analysis in patient cells and mouse CNS

    PMID:36810450 PMID:37759733

    Open questions at the time
    • Mechanism of C-terminal coiled-coil regulation not fully resolved
    • Cholesterol changes lack functional rescue
    • Link between transport cycle and in-cell pathology not directly bridged

Open questions

Synthesis pass · forward-looking unresolved questions
  • How VLCFA accumulation is mechanistically transduced into the diverse downstream phenotypes (ER stress, mitochondrial failure, inflammation, c-MYC loss, cholesterol dysregulation) and what determines the divergent clinical phenotypes remains unresolved.
  • No unifying signaling pathway from VLCFA to phenotype identified
  • Genotype-phenotype determinants unknown
  • Tissue-specific compensation thresholds not fully mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0016787 hydrolase activity 2 GO:0140657 ATP-dependent activity 2 GO:0008289 lipid binding 1
Localization
GO:0005777 peroxisome 2
Pathway
R-HSA-1430728 Metabolism 3
Partners
ABCD2ABCD3

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Positional cloning identified the ALD gene, whose predicted protein (ALDP) shows significant homology to the 70-kDa peroxisomal membrane protein (PMP70) involved in peroxisome biogenesis and belongs to the ATP-binding cassette superfamily, suggesting it encodes a putative peroxisomal transporter involved in import or anchoring of VLCFA-CoA synthetase. Positional cloning; sequence homology analysis Biochimie Medium 8507690
1994 ALDP is a peroxisomal membrane protein: monoclonal antibodies detected a 75 kDa band absent in ALD patients, and immunofluorescence/immunoelectron microscopy localized ALDP to the peroxisomal membrane. Distinct immunofluorescence patterns were observed in Zellweger syndrome cell lines. Monoclonal antibody generation; immunofluorescence; immunoelectron microscopy; Western blot Human molecular genetics High 8004093
1995 ALDP subcellular distribution and abundance examined in ALD patient fibroblasts: 69% of patients lacked punctate peroxisomal immunoreactivity; missense mutations could affect ALDP stability or localization; carboxy-terminal region has a function in stabilizing ALDP. No correlation between immunofluorescence pattern and clinical phenotype was found. Indirect immunofluorescence; mutation analysis in patient fibroblasts American journal of human genetics Medium 7668254
1996 Analysis of 44 ALD kindreds showed that >50% of missense mutations led to complete absence of ALDP immunoreactivity, indicating mutations destabilize the protein; mutations concentrated in/near putative transmembrane segments 2–5, EAA-like motif, and ATP-binding domain. In heterozygous carriers from ALDP-negative kindreds, a mosaic pattern of ALDP-positive and -negative cells was confirmed by X-inactivation. SSCP/denaturing gradient gel electrophoresis; immunocytofluorescence; Western blot of fibroblasts and white blood cells American journal of human genetics Medium 8651290
1996 Absence of truncated ALDP proteins in patients with nonsense/frameshift mutations in the carboxy terminus indicates the carboxy terminus is required for ALDP protein stability. Western blot; mutation analysis in patient fibroblasts Journal of inherited metabolic disease Medium 8892025
1998 4-Phenylbutyrate treatment of X-ALD patient cells and knockout mouse cells increased expression of the closely related peroxisomal protein ALDRP (ABCD2), decreased VLCFA levels, and increased VLCFA beta-oxidation. ALDRP cDNA complementation of X-ALD fibroblasts corrected the biochemical defect, demonstrating functional redundancy between ALDP and ALDRP. cDNA complementation in X-ALD fibroblasts; VLCFA beta-oxidation assay; ALDRP expression analysis; dietary treatment of X-ALD knockout mice Nature medicine High 9809549
1999 ALDP forms homodimers with itself and heterodimers with other peroxisomal ABC proteins (ALDRP, PMP70). cDNA complementation studies suggest overlapping functions among peroxisomal ABC proteins. There are at least two peroxisomal VLCFA-CoA synthetase (VLCS) activities, one ALDP-dependent and one ALDP-independent. Protein dimerization assays (in vitro); cDNA complementation; VLCS activity assays Neurochemical research Medium 10227685
1999 Overexpression of ALDRP (ABCD2) in X-ALD patient fibroblasts restored impaired peroxisomal beta-oxidation and prevented VLCFA accumulation, functionally replacing ALDP. Dietary fenofibrate treatment of ALDP-deficient mice stimulated ALDRP and PMP70 expression and corrected the peroxisomal beta-oxidation defect in liver. Transient and stable cDNA overexpression in X-ALD fibroblasts; peroxisomal beta-oxidation assay; VLCFA measurement; dietary treatment of knockout mice; immunofluorescence Human molecular genetics High 10196381
1999 ALDP expression level is a fundamental determinant of peroxisomal VLCFA beta-oxidation: ALDP overexpression alone restored peroxisomal VLCFA beta-oxidation in SV40T-transformed cells where both acyl-CoA oxidase and ALDP were reduced, demonstrating ALDP acts as a 'gatekeeper' for VLCFA homeostasis. ALDP overexpression in SV40T-transformed cells; peroxisomal beta-oxidation assay; Western blot Molecular genetics and metabolism Medium 10068511
2002 ALDP (and PMP70/ABCD3) bind and hydrolyze ATP: photoaffinity labeling of rat liver peroxisomes showed both proteins bind 8-azido-ATP; Mg2+ promoted ATP hydrolysis to ADP with subsequent ADP dissociation. Both ALDP and PMP70 were also phosphorylated at tyrosine residue(s). Vanadate-induced nucleotide trapping was not observed. Photoaffinity labeling with 8-azido-[α-32P]ATP and 8-azido-[γ-32P]ATP; co-immunoprecipitation; in vitro ATPase assay using rat liver peroxisomes The Journal of biological chemistry High 12176987
2004 In vivo genetic epistasis in ALD-knockout mice: overexpression of ALDRP (ABCD2) prevented both VLCFA accumulation and neurodegenerative features in ALD(-/-) mice. Double knockout (ALD/ALDRP) mice showed earlier onset and more severe disease including inflammatory features compared to ALD single mutants. This demonstrates functional redundancy/overlap between ABCD1 and ABCD2 in vivo. Transgenic mouse overexpression; double knockout mouse model; VLCFA measurement; histopathology; behavioral analysis Human molecular genetics High 15489218
2004 Mouse liver ALDP and PMP70 predominantly form homomeric complexes in vivo: two-step purification and preparative immunoprecipitation of mouse liver peroxisomes showed no evidence of ALDP/PMP70 heterodimers or accessory proteins under normal expression conditions. Protein complex purification from mouse liver peroxisomes; preparative immunoprecipitation; biochemical characterization Biochimica et biophysica acta Medium 15276650
2007 ALDP forms homodimers and ALDP/PMP70 heterodimers in living cells as demonstrated by FRET microscopy. ALDP homodimers predominate. The last 87 C-terminal amino acids are the most important domain mediating these interactions, and the N-terminal transmembrane region provides additional stabilization of ALDP homodimers. Live-cell FRET microscopy; C-terminal deletion constructs; yeast two-hybrid; immunoprecipitation; statistical analysis (PDSA and KS tests) The Journal of biological chemistry High 17609205
2007 Missense mutations in the C-terminal half of ALDP (S606L, R617H, H667D) cause rapid proteasomal degradation; a proteasome inhibitor restored mutant ALDP expression. Wild-type ALDP co-expressed with H667D mutant also disappeared, suggesting dominant-negative degradation after dimerization. The region between transmembrane domains 2 and 3 (e.g., Y174C mutation) is required for peroxisomal targeting of ALDP. Expression of mutant ALDP in X-ALD fibroblasts and CHO cells; proteasome inhibitor treatment; immunofluorescence; Western blot Journal of neurochemistry High 17542813
2008 siRNA-mediated silencing of Abcd1 (and Abcd2) in mouse primary astrocytes caused VLCFA accumulation and triggered an inflammatory response involving NF-κB, AP-1, and C/EBP transcription factors, including induction of iNOS and inflammatory cytokines. Correction of the metabolic defect with monoenoic fatty acids reduced the inflammatory response, directly linking VLCFA accumulation to inflammation. siRNA knockdown in primary mouse astrocytes; VLCFA measurement; inflammatory gene expression; transcription factor analysis; monoenoic fatty acid rescue Journal of lipid research Medium 18723473
2011 ALDRP (ABCD2) and ALDP (ABCD1) physically interact: proximity ligation assay and co-immunoprecipitation demonstrated a direct protein-protein interaction between ALDRP and ALDP. Inactive ALDRP-EGFP exerted a trans-dominant-negative effect on ALDP function, reducing beta-oxidation of C26:0 and C24:0. ALDRP overexpression reduces saturated VLCFA (redundant with ALDP) and specifically promotes DHA (C22:6n-3) metabolism. Proximity ligation assay; co-immunoprecipitation; inducible expression of wild-type and mutant ALDRP-EGFP; fatty acid content analysis in phospholipids; beta-oxidation assays for C26:0, C24:0, and DHA The Journal of biological chemistry High 21209459
2015 ABCD1 deficiency in brain endothelial cells (via siRNA silencing) caused upregulation of adhesion molecules (ICAM1) and downregulation of tight junction proteins (CLDN5) before VLCFA accumulation, mediated through downregulation of the transcription factor c-MYC. MYC silencing mimicked the effects of ABCD1 silencing on CLDN5 and ICAM1 without affecting ABCD1 protein levels, placing c-MYC downstream of ABCD1 but upstream of endothelial barrier function. siRNA silencing of ABCD1 in human brain microvascular endothelial cells; PCR array; Western blot; MYC silencing; monocyte adhesion and transmigration assays Brain : a journal of neurology Medium 26377633
2015 ABCD1 silencing in oligodendrocyte (B12) and astrocyte (U87) cells caused mitochondrial dysfunction: reduced activities of electron transport chain enzymes and TCA cycle enzymes, dysregulated mitochondrial redox status, and disrupted mitochondrial membrane potential. Oligodendrocytes were more severely affected than astrocytes. These perturbations were corrected by HDAC inhibitor SAHA treatment. siRNA knockdown (ABCD1) in B12 and U87 cells; enzyme activity assays (ETC, TCA cycle); mitochondrial membrane potential measurement; ATP quantification; SAHA rescue Journal of neurochemistry Medium 25393703
2019 CRISPR/Cas9 knockout of Abcd1 alone in BV-2 microglial cells did not result in VLCFA accumulation, but combined Abcd1/Abcd2 double knockout caused VLCFA accumulation, lipid inclusions (similar to those in patient brain macrophages), increased cholesterol, and altered expression of microglial genes including Trem2, demonstrating functional redundancy between ABCD1 and ABCD2 specifically in microglia. CRISPR/Cas9 gene editing; VLCFA measurement; electron microscopy; cholesterol/lipid analysis; gene expression analysis Biochimica et biophysica acta. Molecular and cell biology of lipids High 30769094
2021 ABCD1 deficiency results in accumulation of saturated VLCFAs that cause ER stress in ALD fibroblasts, whereas monounsaturated VLCFAs do not. SCD1 (stearoyl-CoA desaturase-1) induction by chloroquine or LXR agonists shifted saturated to monounsaturated VLCFA, reducing lipid toxicity. Abcd1-/y mice treated with LXR agonist showed VLCFA reduction in ALD-relevant tissues, and CRISPR knockout of scd1 in zebrafish mimicked the ALD motor phenotype. Drug screen in zebrafish ALD model; CRISPR scd1 knockout in zebrafish; LXR agonist treatment of Abcd1-/y mice; VLCFA measurement; ER stress assays in ALD fibroblasts; pharmacological SCD1 inhibition The Journal of clinical investigation High 33690217
2023 Cryo-EM structures of ABCD1 in six conformational states (four inward-facing, one outward-facing, plus additional states) revealed: (1) the substrate translocation pathway is formed by two transmembrane domains; (2) two NBDs form the ATP-binding/hydrolysis site; (3) C26:0-CoA substrate binds the TMDs and stimulates NBD ATPase activity; (4) W339 in TM5 is essential for substrate binding and ATP hydrolysis stimulation by substrate; (5) the unique C-terminal coiled-coil domain negatively modulates NBD ATPase activity; (6) in the outward-facing state, ATP binding pulls the two NBDs together and opens the TMDs to the peroxisomal lumen for substrate release. Cryo-electron microscopy (six structures); ATPase activity assays with substrate; site-directed mutagenesis (W339) Signal transduction and targeted therapy High 36810450
2023 ABCD1 deficiency in X-ALD patient fibroblasts and Abcd1-deficient mouse CNS tissues leads to altered cholesterol homeostasis: accumulation of cholesterol esters (CE) containing both saturated VLCFA and mono/polyunsaturated (V)LCFA; increased SOAT1 expression and lipid droplet formation under cholesterol loading; compensatory upregulation of CE hydrolase NCEH1, cholesterol transporter ABCA1, and cholesterol efflux; elevated Apoe and Soat1 in mouse spinal cord. Lipidomics; gene expression analysis; lipid droplet staining; LXR agonist treatment; steroidogenesis assay in X-ALD fibroblasts; immunofluorescence for peroxisome-lipid droplet co-localization Biomolecules Medium 37759733

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet journal of rare diseases 419 22889154
2007 X-linked adrenoleukodystrophy. Nature clinical practice. Neurology 271 17342190
1994 The gene responsible for adrenoleukodystrophy encodes a peroxisomal membrane protein. Human molecular genetics 230 8004093
2001 ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: role in diagnosis and clinical correlations. Human mutation 229 11748843
2012 X-linked adrenoleukodystrophy: clinical, metabolic, genetic and pathophysiological aspects. Biochimica et biophysica acta 207 22483867
1998 Gene redundancy and pharmacological gene therapy: implications for X-linked adrenoleukodystrophy. Nature medicine 201 9809549
2016 Adrenoleukodystrophy - neuroendocrine pathogenesis and redefinition of natural history. Nature reviews. Endocrinology 198 27312864
2013 Pathophysiology of X-linked adrenoleukodystrophy. Biochimie 167 24316281
2004 Functional overlap between ABCD1 (ALD) and ABCD2 (ALDR) transporters: a therapeutic target for X-adrenoleukodystrophy. Human molecular genetics 163 15489218
2006 X-linked adrenoleukodystrophy: clinical, biochemical and pathogenetic aspects. Biochimica et biophysica acta 147 16949688
1999 X-linked adrenoleukodystrophy: genes, mutations, and phenotypes. Neurochemical research 147 10227685
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 133 31909500
2014 X-linked adrenoleukodystrophy: pathogenesis and treatment. Current neurology and neuroscience reports 125 25115486
1999 Adrenoleukodystrophy-related protein can compensate functionally for adrenoleukodystrophy protein deficiency (X-ALD): implications for therapy. Human molecular genetics 122 10196381
1997 X linked adrenoleukodystrophy: clinical presentation, diagnosis, and therapy. Journal of neurology, neurosurgery, and psychiatry 117 9221959
2010 Pathomechanisms underlying X-adrenoleukodystrophy: a three-hit hypothesis. Brain pathology (Zurich, Switzerland) 116 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
2010 General aspects and neuropathology of X-linked adrenoleukodystrophy. Brain pathology (Zurich, Switzerland) 110 20626743
2024 Hematologic Cancer after Gene Therapy for Cerebral Adrenoleukodystrophy. The New England journal of medicine 99 39383458
1999 The neurobiology of X-linked adrenoleukodystrophy, a demyelinating peroxisomal disorder. Trends in neurosciences 97 10088993
1996 Mutational and protein analysis of patients and heterozygous women with X-linked adrenoleukodystrophy. American journal of human genetics 93 8651290
2010 Biochemical aspects of X-linked adrenoleukodystrophy. Brain pathology (Zurich, Switzerland) 86 20626744
2016 Newborn Screening for X-Linked Adrenoleukodystrophy. International journal of neonatal screening 84 31467997
2015 Brain endothelial dysfunction in cerebral adrenoleukodystrophy. Brain : a journal of neurology 70 26377633
2021 Genetic and epigenetic disease modifiers: non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). Translational gastroenterology and hepatology 66 33409397
2024 Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy. The New England journal of medicine 63 39383459
2015 Oxidative stress, mitochondrial and proteostasis malfunction in adrenoleukodystrophy: A paradigm for axonal degeneration. Free radical biology & medicine 62 26073123
1981 The testis in adreno-leukodystrophy. The American journal of pathology 62 7468762
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
2020 The Changing Face of Adrenoleukodystrophy. Endocrine reviews 53 32364223
2018 Impaired plasticity of macrophages in X-linked adrenoleukodystrophy. Brain : a journal of neurology 53 29860501
2002 ATP binding/hydrolysis by and phosphorylation of peroxisomal ATP-binding cassette proteins PMP70 (ABCD3) and adrenoleukodystrophy protein (ABCD1). The Journal of biological chemistry 51 12176987
2007 Distribution and cellular localization of adrenoleukodystrophy protein in human tissues: implications for X-linked adrenoleukodystrophy. Neurobiology of disease 50 17761426
1995 Tumor necrosis factor-alpha and X-linked adrenoleukodystrophy. Journal of neuroimmunology 50 7593551
2022 Treatment of cerebral adrenoleukodystrophy: allogeneic transplantation and lentiviral gene therapy. Expert opinion on biological therapy 48 36107226
2004 Progress in X-linked adrenoleukodystrophy. Current opinion in neurology 48 15167059
2005 X-linked adrenoleukodystrophy: therapeutic approaches to distinct phenotypes. Pediatric transplantation 46 16305618
2020 Extracellular Vesicles in NAFLD/ALD: From Pathobiology to Therapy. Cells 45 32231001
2011 Adrenoleukodystrophy in female heterozygotes: underrecognized and undertreated. Molecular genetics and metabolism 45 22112817
2022 Structure and Function of the ABCD1 Variant Database: 20 Years, 940 Pathogenic Variants, and 3400 Cases of Adrenoleukodystrophy. Cells 42 35053399
2022 Probiotic-derived nanoparticles inhibit ALD through intestinal miR194 suppression and subsequent FXR activation. Hepatology (Baltimore, Md.) 42 35689610
2015 Astrocytes and mitochondria from adrenoleukodystrophy protein (ABCD1)-deficient mice reveal that the adrenoleukodystrophy-associated very long-chain fatty acids target several cellular energy-dependent functions. Biochimica et biophysica acta 42 25583114
2007 Live cell FRET microscopy: homo- and heterodimerization of two human peroxisomal ABC transporters, the adrenoleukodystrophy protein (ALDP, ABCD1) and PMP70 (ABCD3). The Journal of biological chemistry 42 17609205
2004 Mouse liver PMP70 and ALDP: homomeric interactions prevail in vivo. Biochimica et biophysica acta 42 15276650
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
2011 X-linked adrenoleukodystrophy: ABCD1 de novo mutations and mosaicism. Molecular genetics and metabolism 39 21700483
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
2017 Toxic AGE (TAGE) Theory for the Pathophysiology of the Onset/Progression of NAFLD and ALD. Nutrients 38 28632197
2011 Substrate specificity overlap and interaction between adrenoleukodystrophy protein (ALDP/ABCD1) and adrenoleukodystrophy-related protein (ALDRP/ABCD2). The Journal of biological chemistry 37 21209459
2016 Endocrine Dysfunction in X-Linked Adrenoleukodystrophy. Endocrinology and metabolism clinics of North America 36 27241966
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
2024 Lipidomic biomarkers in plasma correlate with disease severity in adrenoleukodystrophy. Communications medicine 32 39256476
2020 Plasma NfL and GFAP as biomarkers of spinal cord degeneration in adrenoleukodystrophy. Annals of clinical and translational neurology 32 33047897
2022 Sex-specific newborn screening for X-linked adrenoleukodystrophy. Journal of inherited metabolic disease 31 36256460
2017 ABCD1 dysfunction alters white matter microvascular perfusion. Brain : a journal of neurology 31 29136088
1996 ALDP expression in fibroblasts of patients with X-linked adrenoleukodystrophy. Journal of inherited metabolic disease 31 8892025
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
2024 Alcohol-related liver disease (ALD): current perspectives on pathogenesis, therapeutic strategies, and animal models. Frontiers in pharmacology 28 39669199
2014 Genotype-phenotype correlation of contiguous gene deletions of SLC6A8, BCAP31 and ABCD1. Clinical genetics 28 24597975
2007 Lack of adrenoleukodystrophy protein enhances oligodendrocyte disturbance and microglia activation in mice with combined Abcd1/Mag deficiency. Acta neuropathologica 28 17828604
2015 An overview of the genetics, mechanisms and management of NAFLD and ALD. Clinical medicine (London, England) 26 26634687
2007 Adrenoleukodystrophy: subcellular localization and degradation of adrenoleukodystrophy protein (ALDP/ABCD1) with naturally occurring missense mutations. Journal of neurochemistry 26 17542813
2006 Immunopathogenesis of adrenoleukodystrophy: current understanding. Journal of neuroimmunology 26 17125847
2024 The role of gut microbiota, exosomes, and their interaction in the pathogenesis of ALD. Journal of advanced research 25 38969094
2005 ABCD1 gene mutations in Chinese patients with X-linked adrenoleukodystrophy. Pediatric neurology 25 16087056
2023 X-linked adrenoleukodystrophy and primary adrenal insufficiency. Frontiers in endocrinology 23 38034003
1993 Adrenoleukodystrophy gene: unexpected homology to a protein involved in peroxisome biogenesis. Biochimie 22 8507690
2017 Antioxidant Capacity and Superoxide Dismutase Activity in Adrenoleukodystrophy. JAMA neurology 21 28288261
1995 Adrenoleukodystrophy: molecular genetics, pathology, and Lorenzo's oil. Brain pathology (Zurich, Switzerland) 21 8520725
2021 Management of adrenoleukodystrophy: From pre-clinical studies to the development of new therapies. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 34560537
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
2001 Eight novel ABCD1 gene mutations and three polymorphisms in patients with X-linked adrenoleukodystrophy: The first polymorphism causing an amino acid exchange. Human mutation 20 11438993
2023 Emerging targets for therapy in ALD: Lessons from NASH. Hepatology (Baltimore, Md.) 19 36938877
2021 ABCD1 and X-linked adrenoleukodystrophy: A disease with a markedly variable phenotype showing conserved neurobiology in animal models. Journal of neuroscience research 19 34716609
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
2023 Structural insights into substrate recognition and translocation of human peroxisomal ABC transporter ALDP. Signal transduction and targeted therapy 17 36810450
2021 Imaging in X-Linked Adrenoleukodystrophy. Neuropediatrics 17 34192790
2010 Adrenoleukodystrophy. Endocrine development 17 21164268
2024 Leriglitazone halts disease progression in adult patients with early cerebral adrenoleukodystrophy. Brain : a journal of neurology 16 38832897
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
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
2017 Therapeutic strategies in adrenoleukodystrophy. Wiener medizinische Wochenschrift (1946) 14 28493141
2012 X-linked adrenoleukodystrophy: molecular and functional analysis of the ABCD1 gene in Argentinean patients. PloS one 14 23300730
2023 ABCD1 Transporter Deficiency Results in Altered Cholesterol Homeostasis. Biomolecules 13 37759733
2022 ABCD1 Gene Mutations: Mechanisms and Management of Adrenomyeloneuropathy. The application of clinical genetics 13 35983253
2019 Association between APOE4 and biomarkers in cerebral adrenoleukodystrophy. Scientific reports 13 31133696

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