ReviewFrontiers in molecular neuroscience2019
Genetic Association of Phosphodiesterases With Human Cognitive Performance.
Review in Frontiers in molecular neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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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.
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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.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- Natural selection and language genes in humans.Scientific reports · 2026Article
- Unveiling the role of phytochemicals in autism spectrum disorder by employing network pharmacology and molecular dynamics simulation.Metabolic brain disease · 2024Article
- PDE4B Missense Variant Increases Susceptibility to Post-traumatic Stress Disorder-Relevant Phenotypes in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Phosphodiesterase and psychiatric disorders: a two-sample Mendelian randomization study.Journal of translational medicine · 2023Article
- Ablation of specific long PDE4D isoforms increases neurite elongation and conveys protection against amyloid-β pathology.Cellular and molecular life sciences : CMLS · 2023Article
- Circadian protein TIMELESS regulates synaptic function and memory by modulating cAMP signaling.Cell reports · 2023Article
- Hypomethylation of the opioid receptor delta 1 gene combined with high opioid receptor delta 1 protein levels indicates increased risk of gout.Journal of clinical laboratory analysis · 2022Article
- Recent developments of phosphodiesterase inhibitors: Clinical trials, emerging indications and novel molecules.Frontiers in pharmacology · 2022Review
- Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders.Molecular psychiatry · 2021Review
- Discovery, Radiolabeling, and Evaluation of Subtype-Selective Inhibitors for Positron Emission Tomography Imaging of Brain Phosphodiesterase-4D.ACS chemical neuroscience · 2020Article
- Protection from AmyloidThe Journal of pharmacology and experimental therapeutics · 2019Article
- Design and Synthesis of Selective Phosphodiesterase 4D (PDE4D) Allosteric Inhibitors for the Treatment of Fragile X Syndrome and Other Brain Disorders.Journal of medicinal chemistry · 2019Article
- Targeting Phosphodiesterases-Towards a Tailor-Made Approach in Multiple Sclerosis Treatment.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Recent, large-scale, genome-wide association studies (GWAS) provide a first view of the genetic fine structure of cognitive performance in healthy individuals. These studies have pooled data from up to 1.1 million subjects based on simple measures of cognitive performance including educational attainment, self-reported math ability, highest math class taken, and pooled, normalized scores from cognitive tests. These studies now allow the genome-wide interrogation of genes and pathways for their potential impact on human cognitive performance. The phosphodiesterase (PDE) enzymes regulate key cyclic nucleotide signaling pathways. Many are expressed in the brain and have been the targets of CNS drug discovery. Genetic variation in PDE1C, PDE4B and PDE4D associates with multiple measures of human cognitive function. The large size of the human PDE4B and PDE4D genes allows genetic fine structure mapping to transcripts encoding dimeric (long) forms of the enzymes. Upstream and downstream effectors of the cAMP pathway modulated by PDE4D [adenylate cyclase 1 (ADCY1), ADCY8, PRKAR1A, CREB1, or CREBBP] did not show genetic association with cognitive performance, however, genetic association was seen with brain derived neurotrophic factor (BDNF), a gene whose expression is modulated by cAMP. Notably absent was genetic association in healthy subjects to targets of CNS drug discovery designed to improve cognition in disease states by the modulation of cholinergic [acetylcholinesterase (ACHE), choline acetyltransferase (CHAT), nicotinic alpha 7 acetylcholine receptor (CHRNA7)], serotonergic (HTR6), histaminergic (HRH3), or glutamatergic (GRM5) pathways. These new data provide a rationale for exploring the therapeutic benefit of selective inhibitors of PDE1C, PDE4B and PDE4D in CNS disorders affecting cognition.
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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.