ArticleCells2019
EGFR/ErbB Inhibition Promotes OPC Maturation up to Axon Engagement by Co-Regulating PIP2 and MBP.
Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
12 citing papers in PubMed, 17 citations in OpenAlex.
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- 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
- Epidermal Growth Factor Pathway in the Age-Related Decline of Oligodendrocyte Regeneration.Frontiers in cellular neuroscience · 2022Review
- Coaxial Electrospun PLLA Fibers Modified with Water-Soluble Materials for Oligodendrocyte Myelination.Polymers · 2021Article
- The Current Challenges for Drug Discovery in CNS Remyelination.International journal of molecular sciences · 2021Review
- Smoothened/AMP-Activated Protein Kinase Signaling in Oligodendroglial Cell Maturation.Frontiers in cellular neuroscience · 2021Article
- Article
- Role of EGFR in the Nervous System.Cells · 2020Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Remyelination in the adult brain relies on the reactivation of the Neuronal Precursor Cell (NPC) niche and differentiation into Oligodendrocyte Precursor Cells (OPCs) as well as on OPC maturation into myelinating oligodendrocytes (OLs). These two distinct phases in OL development are defined by transcriptional and morphological changes. How this differentiation program is controlled remains unclear. We used two drugs that stimulate myelin basic protein (MBP) expression (Clobetasol and Gefitinib) alone or combined with epidermal growth factor receptor (EGFR) or Retinoid X Receptor gamma (RXRγ) gene silencing to decode the receptor signaling required for OPC differentiation in myelinating OLs. Electrospun polystyrene (PS) microfibers were used as synthetic axons to study drug efficacy on fiber engagement. We show that EGFR inhibition per se stimulates MBP expression and increases Clobetasol efficacy in OPC differentiation. Consistent with this, Clobetasol and Gefitinib co-treatment, by co-regulating RXRγ, MBP and phosphatidylinositol 4,5-bisphosphate (PIP2) levels, maximizes synthetic axon engagement. Conversely, RXRγ gene silencing reduces the ability of the drugs to promote MBP expression. This work provides a view of how EGFR/ErbB inhibition controls OPC differentiation and indicates the combination of Clobetasol and Gefitinib as a potent remyelination-enhancing treatment.
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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.