ArticleCell chemical biology2021
Modulation of lanosterol synthase drives 24,25-epoxysterol synthesis and oligodendrocyte formation.
Article in Cell chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Chemical Inhibition of Sterol Biosynthesis.Biomolecules · 2024Pooled it
- Chromatin remodeling factor BAF155 coordinates oligodendroglial-neuronal communications linked to regional myelination and autism-like behavioral deficits in mice.Nature communications · 2025Article
- Ion Mobility-Mass Spectrometry Imaging: Advances in Biomedical Research.Biotech (Basel (Switzerland)) · 2025Review
- CYP51A1 in health and disease: from sterol metabolism to regulated cell death.Cell death discovery · 2025Review
- Multidimensional Uses of Bitter Melon (Current organic synthesis · 2025Review
- Knockouts ofiScience · 2024Article
- Synergistic Effects of PARP Inhibition and Cholesterol Biosynthesis Pathway Modulation.Cancer research communications · 2024Article
- Discovery and Optimization of N-Arylated Tetracyclic Dicarboximides That Target Primary Glioma Stem-like Cells.Journal of medicinal chemistry · 2024Article
- Review
- High-throughput screening for myelination promoting compounds using human stem cell-derived oligodendrocyte progenitor cells.iScience · 2023Article
- Selective and brain-penetrant lanosterol synthase inhibitors target glioma stem-like cells by inducing 24(S),25-epoxycholesterol production.Cell chemical biology · 2023Article
- The interaction between polyphyllin I and SQLE protein induces hepatotoxicity through SREBP-2/HMGCR/SQLE/LSS pathway.Journal of pharmaceutical analysis · 2023Article
- Chronic oligodendrocyte injury in central nervous system pathologies.Communications biology · 2022Review
- The landscape of targets and lead molecules for remyelination.Nature chemical biology · 2022Review
- Enhancers of Human and Rodent Oligodendrocyte Formation Predominantly Induce Cholesterol Precursor Accumulation.ACS chemical biology · 2022Article
- Sterol regulation of developmental and oncogenic Hedgehog signaling.Biochemical pharmacology · 2022Review
- Inhibition of SC4MOL and HSD17B7 shifts cellular sterol composition and promotes oligodendrocyte formation.RSC chemical biology · 2022Article
- 7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19.The Journal of steroid biochemistry and molecular biology · 2021Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Small molecules that promote the formation of new myelinating oligodendrocytes from oligodendrocyte progenitor cells (OPCs) are potential therapeutics for demyelinating diseases. We recently established inhibition of specific cholesterol biosynthesis enzymes and resulting accumulation of 8,9-unsaturated sterols as a unifying mechanism through which many such molecules act. To identify more potent sterol enhancers of oligodendrocyte formation, we synthesized a collection of 8,9-unsaturated sterol derivatives and found that 24,25-epoxylanosterol potently promoted oligodendrocyte formation. In OPCs, 24,25-epoxylanosterol was metabolized to 24,25-epoxycholesterol via the epoxycholesterol shunt pathway. Increasing flux through the epoxycholesterol shunt using genetic manipulation or small-molecule inhibition of lanosterol synthase (LSS) increased endogenous 24,25-epoxycholesterol levels and OPC differentiation. Notably, exogenously supplied 24,25-epoxycholesterol promoted oligodendrocyte formation despite lacking an 8,9-unsaturation. This work highlights epoxycholesterol shunt usage, controlled by inhibitors of LSS, as a target to promote oligodendrocyte formation. Additionally, sterols beyond the 8,9-unsaturated sterols, including 24,25-epoxycholesterol, drive oligodendrocyte formation.
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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.