ArticleThe Journal of clinical investigation2021
Metabolic rerouting via SCD1 induction impacts X-linked adrenoleukodystrophy.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- LipiDecipher: A Structure-Oriented Analytical Framework for Interpretable Clinical Lipidomics.Metabolites · 2026Article
- Adrenoleukodystrophy in adults: phenotypic characterisation and natural history in a large cohort.Journal of neurology, neurosurgery, and psychiatry · 2026Observational
- Evolution of the lipidome uncovers early changes in adrenoleukodystrophy human cortical and spinal organoids.iScience · 2026Article
- An AAV-Based Therapy Approach for Neurological Phenotypes of X-Linked Adrenoleukodystrophy.International journal of molecular sciences · 2025Review
- Review
- Modelling Peroxisomal Disorders in Zebrafish.Cells · 2025Review
- Altered lipid profile and reduced neuronal support in human induced pluripotent stem cell-derived astrocytes from adrenoleukodystrophy patients.Journal of inherited metabolic disease · 2025Article
- Pex1 loss-of-function in zebrafish is viable and recapitulates hallmarks of Zellweger spectrum disorders.Frontiers in molecular neuroscience · 2025Article
- Stearoyl-CoA desaturase-1: a potential therapeutic target for neurological disorders.Molecular neurodegeneration · 2024Review
- From gene to therapy: a review of deciphering the role of ABCD1 in combating X-Linked adrenoleukodystrophy.Lipids in health and disease · 2024Review
- Lipidomic biomarkers in plasma correlate with disease severity in adrenoleukodystrophy.Communications medicine · 2024Article
- Four-dimensional lipidomics profiling in X-linked adrenoleukodystrophy using trapped ion mobility mass spectrometry.Journal of lipid research · 2024Article
- The peroxisome: an update on mysteries 3.0.Histochemistry and cell biology · 2024Review
- Generation and characterization of a zebrafish gain-of-functionFrontiers in pediatrics · 2024Article
- ABCD1 Transporter Deficiency Results in Altered Cholesterol Homeostasis.Biomolecules · 2023Article
- Myelin lipid metabolism and its role in myelination and myelin maintenance.Innovation (Cambridge (Mass.)) · 2023Review
- Peroxisomal defects in microglial cells induce a disease-associated microglial signature.Frontiers in molecular neuroscience · 2023Article
- Targeted Brain Delivery of Dendrimer-4-Phenylbutyrate Ameliorates Neurological Deficits in a Long-Term ABCD1-Deficient Mouse Model of X-Linked Adrenoleukodystrophy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Article
- The Role of Oxidative Stress and Inflammation in X-Link Adrenoleukodystrophy.Frontiers in nutrition · 2022Review
- Insights Into the Peroxisomal Protein Inventory of Zebrafish.Frontiers in physiology · 2022Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
X-linked adrenoleukodystrophy (ALD) is a progressive neurodegenerative disease caused by mutations in ABCD1, the peroxisomal very long-chain fatty acid (VLCFA) transporter. ABCD1 deficiency results in accumulation of saturated VLCFAs. A drug screen using a phenotypic motor assay in a zebrafish ALD model identified chloroquine as the top hit. Chloroquine increased expression of stearoyl-CoA desaturase-1 (scd1), the enzyme mediating fatty acid saturation status, suggesting that a shift toward monounsaturated fatty acids relieved toxicity. In human ALD fibroblasts, chloroquine also increased SCD1 levels and reduced saturated VLCFAs. Conversely, pharmacological inhibition of SCD1 expression led to an increase in saturated VLCFAs, and CRISPR knockout of scd1 in zebrafish mimicked the motor phenotype of ALD zebrafish. Importantly, saturated VLCFAs caused ER stress in ALD fibroblasts, whereas monounsaturated VLCFA did not. In parallel, we used liver X receptor (LXR) agonists to increase SCD1 expression, causing a shift from saturated toward monounsaturated VLCFA and normalizing phospholipid profiles. Finally, Abcd1-/y mice receiving LXR agonist in their diet had VLCFA reductions in ALD-relevant tissues. These results suggest that metabolic rerouting of saturated to monounsaturated VLCFAs may alleviate lipid toxicity, a strategy that may be beneficial in ALD and other peroxisomal diseases in which VLCFAs play a key role.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.