ArticleBritish journal of pharmacology2014
Epac and the high affinity rolipram binding conformer of PDE4 modulate neurite outgrowth and myelination using an in vitro spinal cord injury model.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Roflumilast Inhibits Fibrogenic Activation in Human Intestinal Myofibroblasts via Inhibition of Myocardin-Related Transcription Factor/Serum Response Factor Signaling.International journal of molecular sciences · 2026Article
- TLR3 Knockdown Attenuates Pressure-Induced Neuronal Damage In Vitro.Journal of cellular and molecular medicine · 2024Article
- PDE4D: A Multipurpose Pharmacological Target.International journal of molecular sciences · 2024Review
- EPAC1 enhances brown fat growth and beige adipogenesis.Nature cell biology · 2024Article
- Phosphodiesterase-4 Inhibition in Parkinson's Disease: Molecular Insights and Therapeutic Potential.Cellular and molecular neurobiology · 2023Review
- Ablation of specific long PDE4D isoforms increases neurite elongation and conveys protection against amyloid-β pathology.Cellular and molecular life sciences : CMLS · 2023Article
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- Identification of Regeneration and Hub Genes and Pathways at Different Time Points after Spinal Cord Injury.Molecular neurobiology · 2021Article
- Inhibition of cAMP-phosphodiesterase 4 (PDE4) potentiates the anesthetic effects of Isoflurane in mice.Biochemical pharmacology · 2021Article
- The therapeutic potential of targeting exchange protein directly activated by cyclic adenosine 3',5'-monophosphate (Epac) for central nervous system trauma.Neural regeneration research · 2021Review
- Epac: new emerging cAMP-binding protein.BMB reports · 2021Review
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- Epac2 Elevation Reverses Inhibition by Chondroitin Sulfate ProteoglycansThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Small-molecule allosteric activators of PDE4 long form cyclic AMP phosphodiesterases.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
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- Advances in ex vivo models and lab-on-a-chip devices for neural tissue engineering.Biomaterials · 2019Review
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- Neuroprotective effect of combining tanshinone IIA with low-dose methylprednisolone following acute spinal cord injury in rats.Experimental and therapeutic medicine · 2017Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
background and purposecAMP and pharmacological inhibition of PDE4, which degrades it, are promising therapeutic targets for the treatment of spinal cord injury (SCI). Using our previously described in vitro SCI model, we studied the mechanisms by which cAMP modulators promote neurite outgrowth and myelination using enantiomers of the PDE4-specific inhibitor rolipram and other modulators of downstream signalling effectors. EXPERIMENTAL APPROACH: Rat mixed neural cell myelinating cultures were cut with a scalpel and treated with enantiomers of the PDE4-specific inhibitor rolipram, Epac agonists and PKA antagonists. Neurite outgrowth, density and myelination were assessed by immunocytochemistry and cytokine levels analysed by qPCR. KEY
resultsInhibition of the high-affinity rolipram-binding state (HARBS), rather than the low-affinity rolipram binding state (LARBS) PDE4 conformer promoted neurite outgrowth and myelination. These effects were mediated through the activation of Epac and not through PKA. Expression of the chemokine CXCL10, known to inhibit myelination, was markedly elevated in astrocytes after Rho inhibition and this was blocked by inhibition of Rho kinase or PDE4. CONCLUSIONS AND IMPLICATIONS: PDE4 inhibitors targeted at the HARBS conformer or Epac agonists may provide promising novel targets for the treatment of SCI. Our study demonstrates the differential mechanisms of action of these compounds, as well as the benefit of a combined pharmacological approach and highlighting potential promising targets for the treatment of SCI. These findings need to be confirmed in vivo.
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