ArticleAlzheimer's research & therapy2018
Amyloid β-induced impairments on mitochondrial dynamics, hippocampal neurogenesis, and memory are restored by phosphodiesterase 7 inhibition.
Article in Alzheimer's research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Neurodevelopmental Clues to Neurodegeneration.Pediatric neurology · 2021Pooled it
- Mitochondrial Fusion and Fission in Age-Related Cardio-Cerebral Diseases: Mechanisms and Interventions.Aging cell · 2026Review
- GABA-Induced Exosomes Improve Memory Impairment in Aged Mice.International journal of molecular sciences · 2026Article
- Dihuang Yinzi Regulates cAMP/PKA/CREB-BDNF to Improve Synaptic Plasticity in APP/PS1 Mice: A Study Based on Brain Metabolomics.Chinese journal of integrative medicine · 2025Article
- SENP6 Maintains Mitochondrial Homeostasis by Regulating Mitochondrial Protein Import Through deSUMOylation of TOM40.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Radiosynthesis and Preclinical Evaluation of a Carbon-11 Labeled Phosphodiesterase 7 Inhibitor for PET Neuroimaging.ACS medicinal chemistry letters · 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
- Development of a NovelMolecular pharmaceutics · 2025Article
- Promoting proteostasis by cAMP/PKA and cGMP/PKG.Trends in molecular medicine · 2025Review
- In the Brain of Phosphodiesterases: Potential Therapeutic Targets for Schizophrenia.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2025Review
- Recent Advances in Medicinal Chemistry of Phosphodiesterase 7 Inhibitors and their Potential Therapeutic Applications.Recent advances in inflammation & allergy drug discovery · 2025Review
- Enhancing Proteome Coverage by Using Strong Anion-Exchange in Tandem with Basic-pH Reversed-Phase Chromatography for Sample Multiplexing-Based Proteomics.Journal of proteome research · 2024Article
- Identification of Phosphodiesterase-7A (PDE7A) as a Novel Target for Reducing Ethanol Consumption in Mice.The international journal of neuropsychopharmacology · 2024Article
- Early-life stress and amyloidosis in mice share pathogenic pathways involving synaptic mitochondria and lipid metabolism.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Exercise combined with postbiotics treatment results in synergistic improvement of mitochondrial function in the brain of male transgenic mice for Alzheimer's disease.BMC neuroscience · 2023Article
- JUN upregulation drives aberrant transposable element mobilization, associated innate immune response, and impaired neurogenesis in Alzheimer's disease.Nature communications · 2023Article
- Mitochondrial Complex I and β-Amyloid Peptide Interplay in Alzheimer's Disease: A Critical Review of New and Old Little Regarded Findings.International journal of molecular sciences · 2023Review
- Progranulin Deficiency Induces Mitochondrial Dysfunction in Frontotemporal Lobar Degeneration with TDP-43 Inclusions.Antioxidants (Basel, Switzerland) · 2023Article
- Mechanisms of abnormal adult hippocampal neurogenesis in Alzheimer's disease.Frontiers in neuroscience · 2023Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe phosphodiesterase (PDE) 7 inhibitor S14 is a cell-permeable small heterocyclic molecule that is able to cross the blood-brain barrier. We previously found that intraperitoneal treatment with S14 exerted neuroprotection in an Alzheimer's disease (AD) model (in APP/PS1 mice). The objective of this study was to investigate the neurogenic and cellular effects of oral administration of S14 on amyloid β (Aβ) overload.
methodsWe orally administered the PDE7 inhibitor S14 (15 mg/kg/day) or vehicle in 6-month-old APP/PS1 mice. After 5 weeks of S14 treatment, we evaluated cognitive functions and brain tissues. We also assessed the effects of S14 on the Aβ-treated human neuroblastome SH-SY5Y cell line.
resultsTargeting the cyclic adenosine monophosphate (cAMP)/cAMP-response element binding protein (CREB) pathway, S14 rescued cognitive decline by improving hippocampal neurogenesis in APP/PS1 transgenic mice. Additionally, S14 treatment reverted the Aβ-induced reduction in mitochondrial mass in APP/PS1 mice and in the human neuroblastoma SH-SY5Y cells co-exposed to Aβ. The restoration of the mitochondrial mass was found to be a dual effect of S14: a rescue of the mitochondrial biogenesis formerly slowed down by Aβ overload, and a reduction in the Aβ-increased mitochondrial clearance mechanism of mitophagy.
conclusionsHere, we show new therapeutic effects of the PDE7 inhibitor, confirming S14 as a potential therapeutic drug for AD.
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