ArticleAging cell2014
Modulation of p25 and inflammatory pathways by fisetin maintains cognitive function in Alzheimer's disease transgenic mice.
Article in Aging cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 2 of them syntheses 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
115 citing papers in PubMed, 2 syntheses or guidelines pooled it, 200 citations in OpenAlex.
- The Neuroprotective Role of Fisetin in Different Neurological Diseases: a Systematic Review.Molecular neurobiology · 2023Pooled it
- Nutraceutical Approaches of Autophagy and Neuroinflammation in Alzheimer's Disease: A Systematic Review.Molecules (Basel, Switzerland) · 2020Pooled it
- Enhanced bioavailability and pharmacokinetics of a novel hybrid-hydrogel formulation of fisetin orally administered in healthy individuals: a randomised double-blinded comparative crossover study.Journal of nutritional science · 2022Trial
- Fisetin Attenuates Uterine Leiomyoma in Rats: Potential Crosstalk Between HMGB1, SphK1/S1P, and TGF-β Signaling.Journal of biochemical and molecular toxicology · 2026Article
- Natural Bioactive Compounds Targeting Key Hallmarks of Aging: Functional Food Potential of Spermidine, Fisetin, Berberine, and Urolithin A.Nutrients · 2026Review
- Phytochemicals in Alzheimer's Disease Prevention and Management: Molecular Mechanisms, Therapeutic Potential, Translational Challenges, and Emerging Research Directions.International journal of molecular sciences · 2026Review
- Acid ceramidase modulates the lipid profile and exacerbates sensitivity to ferroptosis in WI-38 replicative senescent cells.Cell death & disease · 2026Article
- Unlocking the Power of Plant-Derived Natural Products: Therapeutic Benefits for Cognitive Health and Neuropsychiatric Symptoms in Dementia-Related Diseases.Plants (Basel, Switzerland) · 2026Review
- Exploring the Senotherapeutic Potential of Polyphenols in Aging and Disease: A Literature Review.International journal of molecular sciences · 2026Review
- Fisetin: a multitarget flavonol bridging oxidative stress, inflammation, aging, and cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Targeting cellular senescence through nutritional senotherapeutics in brain aging and neurodegenerative diseases.Frontiers in nutrition · 2026Review
- Fisetin as a nutritional senotherapeutic: mechanisms, translational promise, and lessons from chronic kidney disease.Frontiers in nutrition · 2026Review
- Surgical removal of visceral adipose tissue has therapeutic benefit in male APPFrontiers in endocrinology · 2026Article
- The role of microbiota modulation in preventing Alzheimer's disease- a review.Pharmacological reports : PR · 2025Review
- Acid ceramidase modulates the lipid profile and exacerbates sensitivity to ferroptosis in senescent cells.Research square · 2025Article
- From Better Diagnostics to Earlier Treatment: The Rapidly Evolving Alzheimer's Disease Landscape.Medicina (Kaunas, Lithuania) · 2025Review
- The impact of fatty acid synthase on HSV-1 infection dynamics.PLoS pathogens · 2025Article
- Fisetin ameliorates vascular smooth muscle cell calcification via DUSP1-dependent p38 MAPK inhibition.Aging · 2025Article
- Senescent brain cell types in Alzheimer's disease: Pathological mechanisms and therapeutic opportunities.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Senolytic intervention improves cognition, metabolism, and adiposity in female APPGeroScience · 2025Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is the most common type of dementia. It is the only one of the top ten causes of death in the USA for which prevention strategies have not been developed. Although AD has traditionally been associated with the deposition of amyloid β plaques and tau tangles, it is becoming increasingly clear that it involves disruptions in multiple cellular systems. Therefore, it is unlikely that hitting a single target will result in significant benefits to patients with AD. An alternative approach is to identify molecules that have multiple biological activities that are relevant to the disease. Fisetin is a small, orally active molecule which can act on many of the target pathways implicated in AD. We show here that oral administration of fisetin to APPswe/PS1dE9 double transgenic AD mice from 3 to 12 months of age prevents the development of learning and memory deficits. This correlates with an increase in ERK phosphorylation along with a decrease in protein carbonylation, a marker of oxidative stress. Importantly, fisetin also reduces the levels of the cyclin-dependent kinase 5 (Cdk5) activator p35 cleavage product, p25, in both control and AD brains. Elevated levels of p25 relative to p35 cause dysregulation of Cdk5 activity leading to neuroinflammation and neurodegeneration. These fisetin-dependent changes correlate with additional anti-inflammatory effects, including alterations in global eicosanoid synthesis, and the maintenance of markers of synaptic function in the AD mice. Together, these results suggest that fisetin may provide a new approach to the treatment of AD.
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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.