ArticleNeurobiology of aging2014
Effect of phosphodiesterase-5 inhibition on apoptosis and beta amyloid load in aged mice.
Article in Neurobiology of aging, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Matrix metalloproteinase 14 modulates diabetes and Alzheimer's disease cross-talk: a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2018Pooled it
- Identifying synergistic combinations of repurposed treatments for Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2025Article
- Drug repurposing for Alzheimer's disease: a Delphi consensus and stakeholder consultation.Alzheimer's research & therapy · 2025Review
- Immunocytochemical Detection of BCL-2 Protein in Chronic B-Cell Lymphoproliferative Disorders.International journal of hematology-oncology and stem cell research · 2025Article
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Experimental modeling of Alzheimer's disease: Translational lessons from cross-taxon analyses.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Phosphodiesterase-5 Inhibitors and Dementia Risk: A Real-World Study.Neuroepidemiology · 2025Article
- Polypharmacological Potential of Phosphodiesterase 5 Inhibitors for the Treatment of Neurocognitive Disorders.Aging and disease · 2024Review
- The Effect of Chronic Treatment with the Inhibitor of Phosphodiesterase 5 (PDE5), Sildenafil, in Combination with L-DOPA on Asymmetric Behavior and Monoamine Catabolism in the Striatum and Substantia Nigra of Unilaterally 6-OHDA-Lesioned Rats.Molecules (Basel, Switzerland) · 2024Article
- Exploring the Multifaceted Potential of Sildenafil in Medicine.Medicina (Kaunas, Lithuania) · 2023Review
- The NO-cGMP-PKG pathway in skeletal remodeling.Annals of the New York Academy of Sciences · 2021Review
- Sildenafil Alleviates Murine Experimental Autoimmune Encephalomyelitis by Triggering Autophagy in the Spinal Cord.Frontiers in immunology · 2021Article
- Could Oral Phosphodiesterase 5 Inhibitors Have a Potential Adjuvant Role in Combating COVID-19 Infection?Sexual medicine reviews · 2021Review
- Therapeutic Potential of Phosphodiesterase Inhibitors against Neurodegeneration: The Perspective of the Medicinal Chemist.ACS chemical neuroscience · 2020Review
- Phosphodiesterase Inhibitors for Alzheimer's Disease: A Systematic Review of Clinical Trials and Epidemiology with a Mechanistic Rationale.Journal of Alzheimer's disease reports · 2020Review
- Sildenafil for the Treatment of Alzheimer's Disease: A Systematic Review.Journal of Alzheimer's disease reports · 2020Review
- Swimming exercise inhibits myocardial ER stress in the hearts of aged mice by enhancing cGMP‑PKG signaling.Molecular medicine reports · 2020Article
- Urolithin A attenuates memory impairment and neuroinflammation in APP/PS1 mice.Journal of neuroinflammation · 2019Article
- Pharmacological manipulation of cGMP and NO/cGMP in CNS drug discovery.Nitric oxide : biology and chemistry · 2019Review
- Fasting and Fast Food Diet Play an Opposite Role in Mice Brain Aging.Molecular neurobiology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Age-related cognitive decline is accompanied by an increase of neuronal apoptosis and a dysregulation of neuroplasticity-related molecules such as brain-derived neurotrophic factor and neurotoxic factors including beta amyloid (Aβ) peptide. Because it has been previously demonstrated that phosphodiesterase-5 inhibitors (PDE5-Is) protect against hippocampal synaptic dysfunction and memory deficits in mouse models of Alzheimer's disease and physiological aging, we investigated the effect of a treatment with the PDE5-I, sildenafil, on cell death, pro- and antiapoptotic molecules, and Aβ production. We demonstrated that chronic intraperitoneal injection of sildenafil (3 mg/kg for 3 weeks) decreased terminal deoxyuridine triphosphate nick end labeling-positive cells in the CA1 hippocampal area of 26-30-month-old mice, downregulating the proapoptotic proteins, caspase-3 and B-cell lymphoma 2-associated X, and increasing antiapoptotic molecules such as B-cell lymphoma protein-2 and brain-derived neurotrophic factor. Also, sildenafil reverted the shifting of amyloid precursor protein processing toward Aβ42 production and the increase of the Aβ42:Aβ40 ratio in aged mice. Our data suggest that PDE5-I might be beneficial to treat age-related detrimental features in a physiological mouse model of aging.
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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.