ArticleScientific reports2017
Memory-enhancing effects of GEBR-32a, a new PDE4D inhibitor holding promise for the treatment of Alzheimer's disease.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 76 citations in OpenAlex.
- [Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Article
- Targeted protein degradation of PDE4 shortforms by a novel proteolysis targeting chimera.The FEBS journal · 2025Article
- Correlation of autophagy and Alzheimer's disease with special emphasis on the role of phosphodiesterase-4.3 Biotech · 2025Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Connecting dots: Preclinical foundations to clinical realities of PDE4 inhibitors in Alzheimer's disease.Inflammopharmacology · 2025Review
- 3D-QSAR Studies on High-affinity Phosphodiestera.Current medicinal chemistry · 2025Article
- Alzheimer's Disease: Exploring the Landscape of Cognitive Decline.ACS chemical neuroscience · 2024Review
- Protective effect of PDE4B subtype-specific inhibition in an App knock-in mouse model for Alzheimer's disease.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- PDE4D: A Multipurpose Pharmacological Target.International journal of molecular sciences · 2024Review
- Early Inhibition of Phosphodiesterase 4B (PDE4B) Instills Cognitive Resilience in APPswe/PS1dE9 Mice.Cells · 2024Article
- Allosteric inhibition of phosphodiesterase 4D induces biphasic memory-enhancing effects associated with learning-activated signaling pathways.Psychopharmacology · 2024Article
- Ablation of specific long PDE4D isoforms increases neurite elongation and conveys protection against amyloid-β pathology.Cellular and molecular life sciences : CMLS · 2023Article
- Arrestin-dependent nuclear export of phosphodiesterase 4D promotes GPCR-induced nuclear cAMP signaling required for learning and memory.Science signaling · 2023Article
- Neuroinflammation in Ischemic Stroke: Inhibition of cAMP-Specific Phosphodiesterases (PDEs) to the Rescue.Biomedicines · 2021Review
- Insight into Inhibitory Mechanism of PDE4D by Dietary Polyphenols Using Molecular Dynamics Simulations and Free Energy Calculations.Biomolecules · 2021Article
- Memory Enhancers for Alzheimer's Dementia: Focus on cGMP.Pharmaceuticals (Basel, Switzerland) · 2021Review
- The Phosphodiesterase-4 Inhibitor Roflumilast, a Potential Treatment for the Comorbidity of Memory Loss and Depression in Alzheimer's Disease: A Preclinical Study in APP/PS1 Transgenic Mice.The international journal of neuropsychopharmacology · 2020Article
- Dominant-Negative Attenuation of cAMP-Selective Phosphodiesterase PDE4D Action Affects Learning and Behavior.International journal of molecular sciences · 2020Article
- Therapeutic Potential of Phosphodiesterase Inhibitors against Neurodegeneration: The Perspective of the Medicinal Chemist.ACS chemical neuroscience · 2020Review
- Insight into GEBR-32a: Chiral Resolution, Absolute Configuration and Enantiopreference in PDE4D Inhibition.Molecules (Basel, Switzerland) · 2020Article
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Authors and funding
14 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Memory loss characterizes several neurodegenerative disorders, including Alzheimer's disease (AD). Inhibition of type 4 phosphodiesterase (PDE4) and elevation of cyclic adenosine monophosphate (cAMP) has emerged as a promising therapeutic approach to treat cognitive deficits. However, PDE4 exists in several isoforms and pan inhibitors cannot be used in humans due to severe emesis. Here, we present GEBR-32a, a new PDE4D full inhibitor that has been characterized both in vitro and in vivo using biochemical, electrophysiological and behavioural analyses. GEBR-32a efficiently enhances cAMP in neuronal cultures and hippocampal slices. In vivo pharmacokinetic analysis shows that GEBR-32a is rapidly distributed within the central nervous system with a very favourable brain/blood ratio. Specific behavioural tests (object location and Y-maze continuous alternation tasks) demonstrate that this PDE4D inhibitor is able to enhance memory in AD transgenic mice and concomitantly rescues their hippocampal long-term potentiation deficit. Of great relevance, our preliminary toxicological analysis indicates that GEBR-32a is not cytotoxic and genotoxic, and does not seem to possess emetic-like side effects. In conclusion, GEBR-32a could represent a very promising cognitive-enhancing drug with a great potential for the treatment of Alzheimer's disease.
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