ArticleBrain : a journal of neurology2015
Brain endothelial dysfunction in cerebral adrenoleukodystrophy.
Article in Brain : a journal of neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 95 citations in OpenAlex.
- The Exercise-CTSS-AD Axis: a novel framework for understanding exercise-induced neuroprotection in Alzheimer's disease.Metabolic brain disease · 2026Review
- Peroxisomal ABCD1 deficiency in mice drives Th1 bias through 25-HC-LXR signaling in CD4Frontiers in immunology · 2026Article
- A scoping review of stem cell models of leukodystrophies: advances in understanding pathophysiological mechanisms.NPJ genomic medicine · 2025Article
- Gene Therapy of Adrenomyeloneuropathy: Challenges, Target Cells, and Prospectives.Biomedicines · 2025Review
- Restoring brain barriers: an innovative approach for treating neurological disorders.Fluids and barriers of the CNS · 2025Review
- Safety and efficacy of leriglitazone in childhood cerebral adrenoleukodystrophy (NEXUS): an interim analysis of an open-label, phase 2/3 trial.EClinicalMedicine · 2025Article
- Review
- A Novel Mouse Model for Cerebral Inflammatory Demyelination in X-Linked Adrenoleukodystrophy: Insights into Pathogenesis and Potential Therapeutic Targets.Annals of neurology · 2025Article
- Optical coherence tomography angiography reveals abnormal retinal vascular density and perfusion in patients with X-linked adrenoleukodystrophy: a cross-sectional study.Orphanet journal of rare diseases · 2025Article
- PPARγ activation ameliorates cognitive impairment and chronic microglial activation in the aftermath of r-mTBI.Journal of neuroinflammation · 2024Article
- Easily misdiagnosed X-linked adrenoleukodystrophy.Italian journal of pediatrics · 2024Article
- The pathology of X-linked adrenoleukodystrophy: tissue specific changes as a clue to pathophysiology.Orphanet journal of rare diseases · 2024Review
- Role of Basal Forebrain Neurons in Adrenomyeloneuropathy in Mice and Humans.Annals of neurology · 2024Article
- Lysosomal cholesterol accumulation is commonly found in most peroxisomal disorders and reversed by 2-hydroxypropyl-β-cyclodextrin.Science China. Life sciences · 2023Article
- Hematopoietic stem-cell gene therapy is associated with restored white matter microvascular function in cerebral adrenoleukodystrophy.Nature communications · 2023Article
- Development of PPARγ Agonists for the Treatment of Neuroinflammatory and Neurodegenerative Diseases: Leriglitazone as a Promising Candidate.International journal of molecular sciences · 2023Review
- Article
- Comprehensive Care to Improve Quality of Life: A Case of Childhood Adrenoleukodystrophy.HCA healthcare journal of medicine · 2022Article
- Low donor chimerism may be sufficient to prevent demyelination in adrenoleukodystrophy.JIMD reports · 2022Article
- Repurposing Vorinostat for the Treatment of Disorders Affecting Brain.Neuromolecular medicine · 2021Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
See Aubourg (doi:10.1093/awv271) for a scientific commentary on this article.X-linked adrenoleukodystrophy is caused by mutations in the ABCD1 gene leading to accumulation of very long chain fatty acids. Its most severe neurological manifestation is cerebral adrenoleukodystrophy. Here we demonstrate that progressive inflammatory demyelination in cerebral adrenoleukodystrophy coincides with blood-brain barrier dysfunction, increased MMP9 expression, and changes in endothelial tight junction proteins as well as adhesion molecules. ABCD1, but not its closest homologue ABCD2, is highly expressed in human brain microvascular endothelial cells, far exceeding its expression in the systemic vasculature. Silencing of ABCD1 in human brain microvascular endothelial cells causes accumulation of very long chain fatty acids, but much later than the immediate upregulation of adhesion molecules and decrease in tight junction proteins. This results in greater adhesion and transmigration of monocytes across the endothelium. PCR-array screening of human brain microvascular endothelial cells after ABCD1 silencing revealed downregulation of both mRNA and protein levels of the transcription factor c-MYC (encoded by MYC). Interestingly, MYC silencing mimicked the effects of ABCD1 silencing on CLDN5 and ICAM1 without decreasing the levels of ABCD1 protein itself. Together, these data demonstrate that ABCD1 deficiency induces significant alterations in brain endothelium via c-MYC and may thereby contribute to the increased trafficking of leucocytes across the blood-brain barrier as seen in cerebral adrenouleukodystrophy.
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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.