ArticleFrontiers in cell and developmental biology2020
A Novel PDE4D Inhibitor BPN14770 Reverses Scopolamine-Induced Cognitive Deficits via cAMP/SIRT1/Akt/Bcl-2 Pathway.
Article in Frontiers in cell and developmental biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Nr4a1 regulates microglia overactivation-mediated neuroinflammation to ameliorate cognitive impairment in trigeminal neuralgia rats.The journal of headache and pain · 2026Article
- Inhibition of the upregulated phosphodiesterase 4D isoforms improves SERCA2a function in diabetic cardiomyopathy.British journal of pharmacology · 2025Article
- Neuroprotective Effects of Cilomilast and Chlorogenic Acid Against Scopolamine-Induced Memory Deficits via Modulation of the cAMP/PKA-CREB-BDNF Pathway.International journal of molecular sciences · 2025Article
- Trps1 regulates mouse zygotic genome activation and preimplantation embryo development via the PDE4D/AKT/CREB signaling pathway.Cell biology and toxicology · 2025Article
- Phosphodiesterase 4 Inhibition in Neuropsychiatric Disorders Associated with Alzheimer's Disease.Cells · 2025Review
- Thymoquinone and aerobic exercise mitigate HFpEF-induced cardiac injury via Apaf1/Cycs axis regulation.Frontiers in pharmacology · 2025Article
- Euonymus hamiltonianus Extract Improves Amnesia in APPswe/Tau Transgenic and Scopolamine-Induced Dementia Models.Molecular neurobiology · 2024Article
- Expression Pattern of PDE4B, PDE4D, and SFRP5 Markers in Colorectal Cancer.Medicina (Kaunas, Lithuania) · 2024Article
- Research progress on phosphodiesterase 4 inhibitors in central nervous system diseases.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- PI3K/AKT signaling activation by roflumilast ameliorates rotenone-induced Parkinson's disease in rats.Inflammopharmacology · 2024Article
- A Molecular Framework for Delirium.The Neurohospitalist · 2024Review
- Differential effects of two phosphodiesterase 4 inhibitors against lipopolysaccharide-induced neuroinflammation in mice.BMC neuroscience · 2023Article
- Cognitive Impairment in Multiple Sclerosis.Bioengineering (Basel, Switzerland) · 2023Review
- High-quality and robust protein quantification in large clinical/pharmaceutical cohorts with IonStar proteomics investigation.Nature protocols · 2023Review
- The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk.Frontiers in immunology · 2023Review
- miR-542-3p-Targeted PDE4D Regulates cAMP/PKA Signaling Pathway and Improves Cardiomyocyte Injury.Contrast media & molecular imaging · 2022Article
- Neurodegeneration, memory loss, and dementia: the impact of biological clocks and circadian rhythm.Frontiers in bioscience (Landmark edition) · 2021Review
- Cognitive Impairment and Dementia: Gaining Insight through Circadian Clock Gene Pathways.Biomolecules · 2021Review
- Bay Leaf (Antioxidants (Basel, Switzerland) · 2021Article
- Phosphodiesterase-4D Knockdown in the Prefrontal Cortex Alleviates Memory Deficits and Synaptic Failure in Mouse Model of Alzheimer's Disease.Frontiers in aging neuroscience · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
A global, quantitative proteomics/systems-biology analysis of the selective pharmacological inhibition of phosphodiesterase-4D (PDE4D) revealed the differential regulation of pathways associated with neuroplasticity in memory-associated brain regions. Subtype selective inhibitors of PDE4D bind in an allosteric site that differs between mice and humans in a single amino acid (tyrosine vs. phenylalanine, respectively). Therefore to study selective inhibition of PDE4D by BPN14770, a subtype selective allosteric inhibitor of PDE4D, we utilized a line of mice in which the PDE4D gene had been humanized by mutating the critical tyrosine to phenylalanine. Relatively low doses of BPN14770 were effective at reversing scopolamine-induced memory and cognitive deficits in humanized PDE4D mice. Inhibition of PDE4D alters the expression of protein kinase A (PKA), Sirt1, Akt, and Bcl-2/Bax which are components of signaling pathways for regulating endocrine response, stress resistance, neuronal autophagy, and apoptosis. Treatment with a series of antagonists, such as H89, sirtinol, and MK-2206, reversed the effect of BPN14770 as shown by behavioral tests and immunoblot analysis. These findings suggest that inhibition of PDE4D enhances signaling through the cAMP-PKA-SIRT1-Akt -Bcl-2/Bax pathway and thereby may provide therapeutic benefit in neurocognitive disorders.
Indexed as
Identifiers
What OpenQuestion holds
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.