ArticleCellular and molecular life sciences : CMLS2013
Inhibition of endogenous phosphodiesterase 7 promotes oligodendrocyte precursor differentiation and survival.
Article in Cellular and molecular life sciences : CMLS, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 57 citations in OpenAlex.
- Article
- The Neurovascular Niche: A Gathering Venue for Neuroinflammation and Remyelination in Multiple Sclerosis.Acta physiologica (Oxford, England) · 2026Review
- Glycogen Synthase Kinase-3β Inhibitor VP3.15 Ameliorates Neurogenesis, Neuronal Loss and Cognitive Impairment in a Model of Germinal Matrix-intraventricular Hemorrhage of the Preterm Newborn.Translational stroke research · 2025Article
- Article
- Mapping the glial transcriptome in Huntington's disease using snRNAseq: selective disruption of glial signatures across brain regions.Acta neuropathologica communications · 2024Article
- Upregulation of Phosphodiesterase 7A Contributes to Concurrent Pain and Depression via Inhibition of cAMP-PKA-CREB-BDNF Signaling and Neuroinflammation in the Hippocampus of Mice.The international journal of neuropsychopharmacology · 2024Article
- Efficacy of a benzothiazole-based LRRK2 inhibitor in oligodendrocyte precursor cells and in a murine model of multiple sclerosis.CNS neuroscience & therapeutics · 2024Article
- Neuronal activity and remyelination: new insights into the molecular mechanisms and therapeutic advancements.Frontiers in cell and developmental biology · 2023Review
- The Dual PDE7-GSK3β Inhibitor, VP3.15, as Neuroprotective Disease-Modifying Treatment in a Model of Primary Progressive Multiple Sclerosis.International journal of molecular sciences · 2022Article
- Ginkgolide B promotes oligodendrocyte precursor cell differentiation and survival via Akt/CREB/bcl-2 signaling pathway after white matter lesion.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- Dynamics of Central Remyelination and Treatment Evolution in a Model of Multiple Sclerosis with Optic Coherence Tomography.International journal of molecular sciences · 2021Article
- Sphingosine-1-Phosphate Receptor Modulators and Oligodendroglial Cells: Beyond Immunomodulation.International journal of molecular sciences · 2020Review
- Functional Heterogeneity of Mouse and Human Brain OPCs: Relevance for Preclinical Studies in Multiple Sclerosis.Journal of clinical medicine · 2020Article
- Targeting Phosphodiesterases-Towards a Tailor-Made Approach in Multiple Sclerosis Treatment.Frontiers in immunology · 2019Review
- R-Ras1 and R-Ras2 Are Essential for Oligodendrocyte Differentiation and Survival for Correct Myelination in the Central Nervous System.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- GD1a Overcomes Inhibition of Myelination by Fibronectin via Activation of Protein Kinase A: Implications for Multiple Sclerosis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Phosphodiesterase Inhibitors as a Therapeutic Approach to Neuroprotection and Repair.International journal of molecular sciences · 2017Review
- Promoting in vivo remyelination with small molecules: a neuroreparative pharmacological treatment for Multiple Sclerosis.Scientific reports · 2017Article
- The Orphan G Protein-coupled Receptor GPR17 Negatively Regulates Oligodendrocyte Differentiation via Gαi/o and Its Downstream Effector Molecules.The Journal of biological chemistry · 2016Article
- PDE7 inhibitor TC3.6 ameliorates symptomatology in a model of primary progressive multiple sclerosis.British journal of pharmacology · 2015Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During the development of the central nervous system (CNS), oligodendrocyte precursors (OPCs) are generated in specific sites within the neural tube and then migrate to colonize the entire CNS, where they differentiate into myelin-forming oligodendrocytes. Demyelinating diseases such as multiple sclerosis (MS) are characterized by the death of these cells. The CNS reacts to demyelination and by promoting spontaneous remyelination, an effect mediated by endogenous OPCs, cells that represent approximately 5-7 % of the cells in the adult brain. Numerous factors influence oligodendrogliogenesis and oligodendrocyte differentiation, including morphogens, growth factors, chemotropic molecules, extracellular matrix proteins, and intracellular cAMP levels. Here, we show that during development and in early adulthood, OPCs in the murine cerebral cortex contain phosphodiesterase-7 (PDE7) that metabolizes cAMP. We investigated the effects of different PDE7 inhibitors (the well-known BRL-50481 and two new ones, TC3.6 and VP1.15) on OPC proliferation, survival, and differentiation. While none of the PDE7 inhibitors analyzed altered OPC proliferation, TC3.6 and VP1.15 enhanced OPC survival and differentiation, processes in which ERK intracellular signaling played a key role. PDE7 expression was also observed in OPCs isolated from adult human brains and the differentiation of these OPCs into more mature oligodendroglial phenotypes was accelerated by treatment with both new PDE7 inhibitors. These findings reveal new roles for PDE7 in regulating OPC survival and differentiation during brain development and in adulthood, and they may further our understanding of myelination and facilitate the development of therapeutic remyelination strategies for the treatment of MS.
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Registered trials
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