ArticleFrontiers in neuroscience2019
Phosphodiesterase 9A in Brain Regulates cGMP Signaling Independent of Nitric-Oxide.
Article in Frontiers in neuroscience, 2019. 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, 25 citations in OpenAlex.
- A single-cell multiomic analysis identifies molecular and gene-regulatory mechanisms dysregulated in developing Down syndrome neocortex.Science (New York, N.Y.) · 2026Article
- TRIM32 promotes tumor immune evasion and impedes Anti-PD-1 treatment by inducing immunosuppressive macrophages in gastric cancer.Journal of translational medicine · 2025Article
- Review
- 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
- Cardiac cGMP Regulation and Therapeutic Applications.Hypertension (Dallas, Tex. : 1979) · 2025Review
- Discovery of Effective Inhibitors Against Phosphodiesterase 9, a Potential Therapeutic Target of Alzheimer's Disease with Antioxidant Capacities.Antioxidants (Basel, Switzerland) · 2025Article
- Epigenetic associations with neonatal age in infants born very preterm, particularly among genes involved in neurodevelopment.Scientific reports · 2024Article
- Virtual Screening-Accelerated Discovery of a Phosphodiesterase 9 Inhibitor with Neuroprotective Effects in the Kainate Toxicity In Vitro Model.ACS chemical neuroscience · 2023Article
- Acute deletion of the central MR/GR steroid receptor correlates with changes in LTP, auditory neural gain, and GC-A cGMP signaling.Frontiers in molecular neuroscience · 2023Article
- BAY-7081: A Potent, Selective, and Orally Bioavailable Cyanopyridone-Based PDE9A Inhibitor.Journal of medicinal chemistry · 2022Article
- Phosphodiesterase 9 inhibition prolongs the antiparkinsonian action of l-DOPA in parkinsonian non-human primates.Neuropharmacology · 2022Article
- Genome-wide association study of idiopathic hypersomnia in a Japanese population.Sleep and biological rhythms · 2022Article
- Inhibition of phosphodiesterase type 9 reduces obesity and cardiometabolic syndrome in mice.The Journal of clinical investigation · 2021Article
- Computational Study on Selective PDE9 Inhibitors on PDE9-Mg/Mg, PDE9-Zn/Mg, and PDE9-Zn/Zn Systems.Biomolecules · 2021Article
- Role of Phosphodiesterase in the Biology and Pathology of Diabetes.International journal of molecular sciences · 2020Review
- cGMP: a unique 2nd messenger molecule - recent developments in cGMP research and development.Naunyn-Schmiedeberg's archives of pharmacology · 2020Review
- Phosphodiesterase 9A Inhibition Facilitates Corticostriatal Transmission in Wild-Type and Transgenic Rats That Model Huntington's Disease.Frontiers in neuroscience · 2020Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PDE9A is a cGMP-specific phosphodiesterase expressed in neurons throughout the brain that has attracted attention as a therapeutic target to treat cognitive disorders. Indeed, PDE9A inhibitors are under evaluation in clinical trials as a treatment for Alzheimer's disease and schizophrenia. However, little is known about the cGMP signaling cascades regulated by PDE9A. Canonical cGMP signaling in brain follows the activation of neuronal nitric oxide synthase (nNOS) and the generation of nitric oxide, which activates soluble guanylyl cyclase and cGMP synthesis. However, we show that in mice, PDE9A regulates a pool of cGMP that is independent of nNOS, specifically, and nitric oxide signaling in general. This PDE9A-regulated cGMP pool appears to be highly compartmentalized and independent of cGMP pools regulated by several PDEs. These findings provide a new foundation for study of the upstream and downstream signaling elements regulated by PDE9A and its potential as a therapeutic target for brain disease.
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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.