ArticleNeurobiology of aging2018
Identification of new PDE9A isoforms and how their expression and subcellular compartmentalization in the brain change across the life span.
Article in Neurobiology of aging, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 40 citations in OpenAlex.
- Structure-Guided Optimization of PDE9A Inhibitors Tackling Neuroinflammation: A Combined Computational and In Vitro Study.ChemMedChem · 2026Article
- Review
- Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 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
- Discovery of Effective Inhibitors Against Phosphodiesterase 9, a Potential Therapeutic Target of Alzheimer's Disease with Antioxidant Capacities.Antioxidants (Basel, Switzerland) · 2025Article
- Phosphodiesterases: Evolving Concepts and Implications for Human Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- Biologic that disrupts PDE11A4 homodimerization in hippocampus CA1 reverses age-related cognitive decline of social memories in mice.Neurobiology of aging · 2023Article
- 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
- Pharmacological modulation of phosphodiesterase-7 as a novel strategy for neurodegenerative disorders.Inflammopharmacology · 2022Review
- Conserved age-related increases in hippocampal PDE11A4 cause unexpected proteinopathies and cognitive decline of social associative memories.Aging cell · 2022Article
- A genetic basis for friendship? Homophily for membrane-associated PDE11A-cAMP-CREB signaling in CA1 of hippocampus dictates mutual social preference in male and female mice.Molecular psychiatry · 2021Article
- Aging triggers an upregulation of a multitude of cytokines in the male and especially the female rodent hippocampus but more discrete changes in other brain regions.Journal of neuroinflammation · 2021Article
- Current Modulation of Guanylate Cyclase Pathway Activity-Mechanism and Clinical Implications.Molecules (Basel, Switzerland) · 2021Review
- A Perspective on Natural and Nature-Inspired Small Molecules Targeting Phosphodiesterase 9 (PDE9): Chances and Challenges against Neurodegeneration.Pharmaceuticals (Basel, Switzerland) · 2021Review
- The Role of PDE11A4 in Social Isolation-Induced Changes in Intracellular Signaling and Neuroinflammation.Frontiers in pharmacology · 2021Article
- Phosphodiesterases PDE2A and PDE10A both change mRNA expression in the human brain with age, but only PDE2A changes in a region-specific manner with psychiatric disease.Cellular signalling · 2020Article
- Phosphodiesterase 9A Inhibition Facilitates Corticostriatal Transmission in Wild-Type and Transgenic Rats That Model Huntington's Disease.Frontiers in neuroscience · 2020Article
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
3',5'-Cyclic nucleotide phosphodiesterases (PDEs) degrade 3',5' cyclic adenonosine monophosphate (cAMP) and 3',5' cyclic guanosine monophosphate (cGMP), with PDE9A having the highest affinity for cGMP. We show PDE9A6 and 3 novel PDE9 isoforms (PDE9X-100, PDE9X-120, and PDE9X-175) are reliably detected in the brain and lung of mice, whereas PDE9A2 and other isoforms are found elsewhere. PDE9A localizes to the membrane in all organs except the bladder, where it is cytosolic. Brain additionally shows PDE9 in the nuclear fraction. PDE9A mRNA expression/localization dramatically changes across neurodevelopment in a manner that is strikingly consistent between mice and humans (i.e., decreased expression in the hippocampus and cortex and inverted-U in the cerebellum). Study of the 4 PDE9 isoforms in the mouse brain from postnatal day 7 through 24 months similarly identifies dramatic effects of age on expression and subcellular compartmentalization that are isoform specific and brain region specific. Finally, PDE9A mRNA is elevated in the aged human hippocampus with dementia when there is a history of traumatic brain injury. Thus, brain PDE9 is localized to preferentially regulate nuclear- and membrane-proximal pools of cGMP, and its function likely changes across the life span.
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