ArticleBrain : a journal of neurology2021
BMP receptor blockade overcomes extrinsic inhibition of remyelination and restores neurovascular homeostasis.
Article in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Beyond the barrier: Targeting blood-brain interactions for neuroprotection and repair.Neural regeneration research · 2026Article
- Routes of precursors' migration in remyelination.Brain : a journal of neurology · 2026Review
- Extending the Branches of Neonatal Neurocritical Care.Seminars in perinatology · 2025Review
- Disruption of DNA methylation underpins the neuroinflammation induced by targeted CNS radiotherapy.Brain : a journal of neurology · 2025Article
- Review
- Blood-brain barrier disruption: a culprit of cognitive decline?Fluids and barriers of the CNS · 2024Review
- Fibrinogen inhibits sonic hedgehog signaling and impairs neonatal cerebellar development after blood-brain barrier disruption.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Fibrin promotes oxidative stress and neuronal loss in traumatic brain injury via innate immune activation.Journal of neuroinflammation · 2024Article
- Conversion of Astrocyte Cell Lines to Oligodendrocyte Progenitor Cells Using Small Molecules and Transplantation to Animal Model of Multiple Sclerosis.Journal of molecular neuroscience : MN · 2024Article
- Defining blood-induced microglia functions in neurodegeneration through multiomic profiling.Nature immunology · 2023Article
- Arginine vasopressin hormone receptor antagonists in experimental autoimmune encephalomyelitis rodent models: A new approach for human multiple sclerosis treatment.Frontiers in neuroscience · 2023Review
- Infiltrating circulating monocytes provide an important source of BMP4 at the early stage of spinal cord injury.Disease models & mechanisms · 2023Article
- Lysophosphatidic acid signaling via LPAJournal of neurochemistry · 2022Article
- Review
- Breaking the barriers to remyelination in multiple sclerosis.Current opinion in pharmacology · 2022Review
- Pathways to cures for multiple sclerosis: A research roadmap.Multiple sclerosis (Houndmills, Basingstoke, England) · 2022Article
- Dysregulation of BMP, Wnt, and Insulin Signaling in Fragile X Syndrome.Frontiers in cell and developmental biology · 2022Review
- Regulation of Myostatin on the Growth and Development of Skeletal Muscle.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Extrinsic inhibitors at sites of blood-brain barrier disruption and neurovascular damage contribute to remyelination failure in neurological diseases. However, therapies to overcome the extrinsic inhibition of remyelination are not widely available and the dynamics of glial progenitor niche remodelling at sites of neurovascular dysfunction are largely unknown. By integrating in vivo two-photon imaging co-registered with electron microscopy and transcriptomics in chronic neuroinflammatory lesions, we found that oligodendrocyte precursor cells clustered perivascularly at sites of limited remyelination with deposition of fibrinogen, a blood coagulation factor abundantly deposited in multiple sclerosis lesions. By developing a screen (OPC-X-screen) to identify compounds that promote remyelination in the presence of extrinsic inhibitors, we showed that known promyelinating drugs did not rescue the extrinsic inhibition of remyelination by fibrinogen. In contrast, bone morphogenetic protein type I receptor blockade rescued the inhibitory fibrinogen effects and restored a promyelinating progenitor niche by promoting myelinating oligodendrocytes, while suppressing astrocyte cell fate, with potent therapeutic effects in chronic models of multiple sclerosis. Thus, abortive oligodendrocyte precursor cell differentiation by fibrinogen is refractory to known promyelinating compounds, suggesting that blockade of the bone morphogenetic protein signalling pathway may enhance remyelinating efficacy by overcoming extrinsic inhibition in neuroinflammatory lesions with vascular damage.
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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.