ArticleClinical epigenetics2015
Concomitant histone deacetylase and phosphodiesterase 5 inhibition synergistically prevents the disruption in synaptic plasticity and it reverses cognitive impairment in a mouse model of Alzheimer's disease.
Article in Clinical epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Anticancer drugs repurposed for Alzheimer's disease: a systematic review.Alzheimer's research & therapy · 2021Pooled it
- Epigenetic Modulation Is a Key Mechanism in Cognitive Deficit: Unveiling Garcinol as a Potent HAT Inhibitor in Improving Alzheimer's Disease.ACS omega · 2026Review
- Proof-of-concept study: APOE4 brain endothelial cells as a phenotypic compound screen.Alzheimer's research & therapy · 2026Article
- Exploring Autophagy Inducing Molecules: Targeting Diverse Pathways in Alzheimer's Disease Management.Medicinal research reviews · 2026Review
- Computer-aided Drug Design for Alzheimer's Disease: Recent Advancements and Future Perspectives.Current topics in medicinal chemistry · 2026Review
- An overview on pharmaceutical applications of phosphodiesterase enzyme 5 (PDE5) inhibitors.Molecular diversity · 2025Review
- Polypharmacological Potential of Phosphodiesterase 5 Inhibitors for the Treatment of Neurocognitive Disorders.Aging and disease · 2024Review
- Review
- Alzheimer's Disease-Related Epigenetic Changes: Novel Therapeutic Targets.Molecular neurobiology · 2024Review
- Unlocking the epigenetic symphony: histone acetylation's impact on neurobehavioral change in neurodegenerative disorders.Epigenomics · 2024Review
- Deciphering the Mysterious Relationship between the Cross-Pathogenetic Mechanisms of Neurodegenerative and Oncological Diseases.International journal of molecular sciences · 2023Review
- Small molecule modulators of chromatin remodeling: from neurodevelopment to neurodegeneration.Cell & bioscience · 2023Review
- Defective synaptic plasticity in a model of Coffin-Lowry syndrome is rescued by simultaneously targeting PKA and MAPK pathways.Learning & memory (Cold Spring Harbor, N.Y.) · 2022Article
- A Class I HDAC Inhibitor BG45 Alleviates Cognitive Impairment through the CaMKII/ITPKA/CaPharmaceuticals (Basel, Switzerland) · 2022Article
- Age-dependent attenuation of spatial memory deficits by the histone acetyltransferase p300/CBP-associated factor (PCAF) in 3xTG Alzheimer's disease mice.Learning & memory (Cold Spring Harbor, N.Y.) · 2022Article
- Inhibition of phosphodiesterase: A novel therapeutic target for the treatment of mild cognitive impairment and Alzheimer's disease.Frontiers in aging neuroscience · 2022Review
- Repurposing Vorinostat for the Treatment of Disorders Affecting Brain.Neuromolecular medicine · 2021Review
- A putative role for lncRNAs in epigenetic regulation of memory.Neurochemistry international · 2021Review
- Chromatin Alterations in Neurological Disorders and Strategies of (Epi)Genome Rescue.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Shifting the paradigm in treating multi-factorial diseases: polypharmacological co-inhibitors of HDAC6.RSC medicinal chemistry · 2021Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGiven the implication of histone acetylation in memory processes, histone deacetylase inhibitors (HDACIs) have been postulated as potential modulators of cognitive impairment in Alzheimer's disease (AD). However, dose-dependent side effects have been described in patients with the currently available broad-spectrum HDACIs, explaining why their therapeutic potential has not been realized for chronic diseases. Here, by simultaneously targeting two independent enzyme activities, histone deacetylase (HDAC) and phosphodiesterase-5 (PDE5), we propose a novel mode of inhibitory action that might increase the therapeutic specificity of HDACIs.
resultsThe combination of vorinostat, a pan-HDACI, and tadalafil, a PDE5 inhibitor, rescued the long-term potentiation impaired in slices from APP/PS1 mice. When administered in vivo, the combination of these drugs alleviated the cognitive deficits in AD mice, as well as the amyloid and tau pathology, and it reversed the reduced dendritic spine density on hippocampal neurons. Significantly, the combination of vorinostat and tadalafil was more effective than each drug alone, both against the symptoms and in terms of disease modification, and importantly, these effects persisted after a 4-week washout period.
conclusionsThe results highlight the pharmacological potential of a combination of molecules that inhibit HDAC and PDE5 as a therapeutic approach for AD treatment.
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