ArticleThe Journal of clinical investigation2020
Mature myelin maintenance requires Qki to coactivate PPARβ-RXRα-mediated lipid metabolism.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.
- Identification of Key Genes and Regulatory Pathways in Multiple Sclerosis Brain Samples: A Meta-Analysis of Micro-Array Datasets.International journal of molecular sciences · 2023Pooled it
- Single cell landscape of sex differences in the different courses of multiple sclerosis.Biology of sex differences · 2026Article
- Epithelial QKI Protects Against Emphysema by Maintaining Mitochondrial Integrity.bioRxiv : the preprint server for biology · 2026Article
- Rewiring Lipid Metabolism: PINK1 as a Central Regulator of Mitochondrial Homeostasis in Parkinson's Disease.International journal of molecular sciences · 2026Review
- Oligodendrocyte Piezo2 is a regulator of age-dependent myelin integrity and dysregulated in multiple sclerosis.Communications biology · 2026Article
- Monocarboxylate transporter 2 regulates maintenance of myelin and axonal integrity by oligodendrocytes.Nature communications · 2026Article
- SNAP-23 mediated vesicular trafficking in oligodendrocytes is necessary to maintain adult myelin integrity in mice.Nature communications · 2026Article
- Clemastine Restores Myelination Protein Expression in S16 Schwann Cells by Enhancing AMPK Activation and Reducing HBiomolecules & therapeutics · 2026Article
- From lipid function to dysfunction: Very long-chain fatty acids as emerging regulators of neuroinflammatory pathways.iScience · 2026Review
- RNA-Binding Proteins in Adipose Biology: From Mechanistic Understanding to Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Metabolic signatures in sciatic nerve of PMP22 transgenic rats provide insights into the pathogenesis of charcot-marie-tooth disease type 1 A.Scientific reports · 2026Article
- Navigating the Lipid Landscape: The Role of Fatty Acid Synthase in Neural Stem Cell Fate and Central Nervous System Function.Molecular neurobiology · 2025Review
- Quaking Protein in Myelin Maintenance and Regeneration in the Central Nervous System.Molecular neurobiology · 2025Review
- Lipid metabolism in health and disease: Mechanistic and therapeutic insights for Parkinson's disease.Chinese medical journal · 2025Review
- Seipin Deficiency Impairs Motor Coordination in Mice by Compromising Spinal Cord Myelination.Neuromolecular medicine · 2025Article
- NF-κB RelA regulates temporal oligodendrocyte differentiation in the postnatal brains.Frontiers in cellular neuroscience · 2025Article
- Article
- Targeting the Hippo pathway in Schwann cells ameliorates peripheral nerve degeneration via a polypharmacological mechanism.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Oligodendroglial fatty acid metabolism as a central nervous system energy reserve.Nature neuroscience · 2024Article
- Dynamics of mature myelin.Nature neuroscience · 2024Review
Corrections and comments
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Authors and funding
21 authors at 9 institutions in 3 countries.
Funding
Abstract
Lipid-rich myelin forms electrically insulating, axon-wrapping multilayers that are essential for neural function, and mature myelin is traditionally considered metabolically inert. Surprisingly, we discovered that mature myelin lipids undergo rapid turnover, and quaking (Qki) is a major regulator of myelin lipid homeostasis. Oligodendrocyte-specific Qki depletion, without affecting oligodendrocyte survival, resulted in rapid demyelination, within 1 week, and gradually neurological deficits in adult mice. Myelin lipids, especially the monounsaturated fatty acids and very-long-chain fatty acids, were dramatically reduced by Qki depletion, whereas the major myelin proteins remained intact, and the demyelinating phenotypes of Qki-depleted mice were alleviated by a high-fat diet. Mechanistically, Qki serves as a coactivator of the PPARβ-RXRα complex, which controls the transcription of lipid-metabolism genes, particularly those involved in fatty acid desaturation and elongation. Treatment of Qki-depleted mice with PPARβ/RXR agonists significantly alleviated neurological disability and extended survival durations. Furthermore, a subset of lesions from patients with primary progressive multiple sclerosis were characterized by preferential reductions in myelin lipid contents, activities of various lipid metabolism pathways, and expression level of QKI-5 in human oligodendrocytes. Together, our results demonstrate that continuous lipid synthesis is indispensable for mature myelin maintenance and highlight an underappreciated role of lipid metabolism in demyelinating diseases.
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