ArticleACS chemical neuroscience2014
Crosstalk between phosphodiesterase 7 and glycogen synthase kinase-3: two relevant therapeutic targets for neurological disorders.
Article in ACS chemical neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- VP3.15, a dual GSK-3β/PDE7 inhibitor, reduces glioblastoma tumor growth though changes in the tumor microenvironment in a PTEN wild-type context.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Downregulation of CMIP contributes to preeclampsia development by impairing trophoblast function via the PDE7B-cAMP pathway.Cellular and molecular life sciences : CMLS · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- 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
- Unleashing Spinal Cord Repair: The Role of cAMP-Specific PDE Inhibition in Attenuating Neuroinflammation and Boosting Regeneration after Traumatic Spinal Cord Injury.International journal of molecular sciences · 2023Review
- C/EBPβ Regulates TFAM Expression, Mitochondrial Function and Autophagy in Cellular Models of Parkinson's Disease.International journal of molecular sciences · 2023Article
- Pharmacological modulation of phosphodiesterase-7 as a novel strategy for neurodegenerative disorders.Inflammopharmacology · 2022Review
- 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
- Therapeutic Potential of Phosphodiesterase Inhibitors against Neurodegeneration: The Perspective of the Medicinal Chemist.ACS chemical neuroscience · 2020Review
- Phosphodiesterase 7 Regulation in Cellular and Rodent Models of Parkinson's Disease.Molecular neurobiology · 2020Article
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- Modulation of GSK-3 provides cellular and functional neuroprotection in the rd10 mouse model of retinitis pigmentosa.Molecular neurodegeneration · 2018Article
- The direct and indirect effects of α-synuclein on microtubule stability in the pathogenesis of Parkinson's disease.Neuropsychiatric disease and treatment · 2018Review
- 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
- CCAAT/enhancer binding protein β directly regulates the expression of the complement component 3 gene in neural cells: implications for the pro-inflammatory effects of this transcription factor.Journal of neuroinflammation · 2015Article
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Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic neuroinflammation has been increasingly recognized as a primary mechanism underlying acute brain injury and neurodegenerative diseases. Enhanced expression of diverse pro-inflammatory agents in glial cells has been shown to contribute to the cell death that takes place in these disorders. Previous data from our group have shown that different inhibitors of the cyclic adenosine monophosphate (cAMP) specific phosphodiesterase 7 (PDE7) and glycogen synthase kinase-3 (GSK-3) enzymes are potent anti-inflammatory agents in different models of brain injury. In this study, we investigated cross-talk between PDE7 and GSK-3, two relevant therapeutic targets for neurological disorders, using a chemical approach. To this end, we compared specific inhibitors of GSK-3 and PDE7 with dual inhibitors of both enzymes with regard to anti-inflammatory effects in primary cultures of glial cells treated with lipopolysaccharide. Our results show that the GSK-3 inhibitors act exclusively by inhibition of this enzyme. By contrast, PDE7 inhibitors exert their effects via inhibition of PDE7 to increase intracellular cAMP levels but also through indirect inhibition of GSK-3. Activation of protein kinase A by cAMP results in phosphorylation of Ser9 of GSK-3 and subsequent inhibition. Our results indicate that the indirect inhibition of GSK-3 by PDE7 inhibitors is an important mechanism that should be considered in the future development of pharmacological treatments.
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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.