ArticleACS chemical biology2022
Enhancers of Human and Rodent Oligodendrocyte Formation Predominantly Induce Cholesterol Precursor Accumulation.
Article in ACS chemical biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Chemical Inhibition of Sterol Biosynthesis.Biomolecules · 2024Pooled it
- Oligodendrocyte dysfunction in neurodegenerative diseases: pathological features, underlying mechanisms and therapeutic targeting.Frontiers in aging neuroscience · 2026Review
- An In Silico Study on Withania somnifera Bioactives and Curcumin Analogs as Potential Inducers of Smoothened (Smo) Receptor of Sonic Hedgehog (SHH) Pathway to Promote Oligodendrogenesis.Molecular neurobiology · 2025Article
- Regulation of CNS Lipids by Protease Activated Receptor 1.Journal of neurochemistry · 2025Article
- Remyelinating Drugs at a Crossroad: How to Improve Clinical Efficacy and Drug Screenings.Cells · 2024Review
- Pelizaeus-Merzbacher disease: on the cusp of myelin medicine.Trends in molecular medicine · 2024Review
- The Cholesterol-5,6-Epoxide Hydrolase: A Metabolic Checkpoint in Several Diseases.Advances in experimental medicine and biology · 2024Article
- Pharmacological targeting of smoothened receptor cysteine-rich domain by Budesonide promotesFrontiers in molecular neuroscience · 2024Article
- N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation.Cells · 2023Article
- The landscape of targets and lead molecules for remyelination.Nature chemical biology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Regeneration of myelin in the central nervous system is being pursued as a potential therapeutic approach for multiple sclerosis. Several labs have reported small molecules that promote oligodendrocyte formation and remyelination in vivo. Recently, we reported that many such molecules function by inhibiting a narrow window of enzymes in the cholesterol biosynthesis pathway. Here we describe a new high-throughput screen of 1,836 bioactive molecules and a thorough re-analysis of more than 60 molecules previously identified as promoting oligodendrocyte formation from human, rat, or mouse oligodendrocyte progenitor cells. These studies highlight that an overwhelming fraction of validated screening hits, including several molecules being evaluated clinically for remyelination, inhibit cholesterol pathway enzymes like emopamil-binding protein (EBP). To rationalize these findings, we suggest a model that relies on the high druggability of sterol-metabolizing enzymes and the ability of cationic amphiphiles to mimic the transition state of EBP. These studies further establish cholesterol pathway inhibition as a dominant mechanism among screening hits that enhance human, rat, or mouse 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.