ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Interplay between LXR and Wnt/β-catenin signaling in the negative regulation of peripheral myelin genes by oxysterols.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. 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, 88 citations in OpenAlex.
- A Validated Mass Spectrometry Platform for Oxysterol Analysis of Single Human Gastruloids and Liver Organoids.Analytical chemistry · 2026Article
- Oxysterol signaling in the central nervous system: cellular mechanisms and implications for neurodegeneration.Frontiers in molecular neuroscience · 2026Review
- Thrombin increases the expression of cholesterol 25-hydroxylase in rat astrocytes after spinal cord injury.Neural regeneration research · 2023Article
- Liver X Receptor Regulation of Glial Cell Functions in the CNS.Biomedicines · 2022Review
- 25-Hydroxycholesterol as a Signaling Molecule of the Nervous System.Biochemistry. Biokhimiia · 2022Review
- Review: Myelin clearance is critical for regeneration after peripheral nerve injury.Frontiers in neurology · 2022Review
- Expression of Ripk1 and DAM genes correlates with severity and progression of Krabbe disease.Human molecular genetics · 2021Article
- Mechanisms and Treatments in Demyelinating CMT.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Overexpression of Foxc1 regenerates crushed rat facial nerves by promoting Schwann cells migration via the Wnt/β-catenin signaling pathway.Journal of cellular physiology · 2020Article
- Cholesterol 25-hydroxylase protects against experimental colitis in mice by modulating epithelial gut barrier function.Scientific reports · 2020Article
- ABCA1/ApoE/HDL Signaling Pathway Facilitates Myelination and Oligodendrogenesis after Stroke.International journal of molecular sciences · 2020Article
- Neuronal LXR Regulates Neuregulin 1 Expression and Sciatic Nerve-Associated Cell Signaling in Western Diet-fed Rodents.Scientific reports · 2020Article
- Regulating PMP22 expression as a dosage sensitive neuropathy gene.Brain research · 2020Review
- Liver X Receptors and Their Implications in the Physiology and Pathology of the Peripheral Nervous System.International journal of molecular sciences · 2019Review
- Regulation of Brain Cholesterol: What Role Do Liver X Receptors Play in Neurodegenerative Diseases?International journal of molecular sciences · 2019Review
- Mediation of antiinflammatory effects of Rg3-enriched red ginseng extract from Korean Red Ginseng via retinoid X receptor α-peroxisome-proliferating receptor γ nuclear receptors.Journal of ginseng research · 2019Article
- Exome sequencing in multiple sclerosis families identifies 12 candidate genes and nominates biological pathways for the genesis of disease.PLoS genetics · 2019Article
- Epstein-Barr Virus Induced Gene-2 Upregulation Identifies a Particular Subtype of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.Frontiers in pediatrics · 2019Review
- An innate immune response and altered nuclear receptor activation defines the spinal cord transcriptome during alpha-tocopherol deficiency in Ttpa-null mice.Free radical biology & medicine · 2018Article
- Liver X Receptor exerts a protective effect against the oxidative stress in the peripheral nerve.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxysterols are reactive molecules generated from the oxidation of cholesterol. Their implication in cholesterol homeostasis and in the progression of neurodegenerative disorders is well known, but few data are available for their functions in the peripheral nervous system. Our aim was to study the influence of oxysterols on myelin gene expression and myelin sheath formation in peripheral nerves. We show by gas chromatography/mass spectrometry that Schwann cells and sciatic nerves contain 24(S)-hydroxycholesterol, 25-hydroxycholesterol, and 27-hydroxycholesterol and that they express their biosynthetic enzymes and receptors (liver X receptors LXRα and LXRβ). We demonstrate that oxysterols inhibit peripheral myelin gene expression [myelin protein zero (MPZ) and peripheral myelin protein-22 (PMP22)] in a Schwann cell line. This downregulation is mediated by either LXRα or LXRβ, depending on the promoter context, as suggested by siRNA strategy and chromatin immunoprecipitation assays in Schwann cells and in the sciatic nerve of LXR knock-out mice. Importantly, the knock-out of LXR in mice results in thinner myelin sheaths surrounding the axons. Oxysterols repress myelin genes via two mechanisms: by binding of LXRs to myelin gene promoters and by inhibiting the Wnt/β-catenin pathway that is crucial for the expression of myelin genes. The Wnt signaling components (Disheveled, TCF/LEF, β-catenin) are strongly repressed by oxysterols. Furthermore, the recruitment of β-catenin at the levels of the MPZ and PMP22 promoters is decreased. Our data reveal new endogenous mechanisms for the negative regulation of myelin gene expression, highlight the importance of oxysterols and LXR in peripheral nerve myelination, and open new perspectives of treating demyelinating diseases with LXR agonists.
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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.