ArticleJournal of cell science2016
Cdk5-Foxo3 axis: initially neuroprotective, eventually neurodegenerative in Alzheimer's disease models.
Article in Journal of cell science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Circulating insulin-like growth factors and Alzheimer disease: A mendelian randomization study.Neurology · 2018Pooled it
- Article
- FOXO family and neurodegenerative diseases: Mechanisms of action and therapeutic potential.Redox biology · 2026Review
- FOXO transcription factors in Alzheimer's Disease: balancing neuroprotection and neuronal degeneration.Molecular biology reports · 2026Review
- Novel genetic variants identification and immune profiling in ataxia telangiectasia patients.Journal of translational medicine · 2026Article
- Dual targeting of the UPS and autophagy as a novel therapy for neurodegenerative proteinopathies.Frontiers in cellular neuroscience · 2026Review
- FOXOs and their roles in acute and chronic neurological disorders.Frontiers in molecular biosciences · 2025Review
- Exploring Therapeutic Strategies: The Relationship between Metabolic Disorders and FOXO Signalling in Alzheimer's Disease.CNS & neurological disorders drug targets · 2025Review
- Effects of the therapeutic correction of U1 snRNP complex on Alzheimer's disease.Scientific reports · 2024Article
- Article
- Regulation of mitochondrial function by FOXOs in ischemic stroke and Alzheimer's disease.Organelle (Tucson, Ariz.) · 2024Article
- The role of Foxo3a in neuron-mediated cognitive impairment.Frontiers in molecular neuroscience · 2024Review
- CDK5: an oncogene or an anti-oncogene: location location location.Molecular cancer · 2023Review
- CDK10, CDK11, FOXO1, and FOXO3 Gene Expression in Alzheimer's Disease Encephalic Samples.Cellular and molecular neurobiology · 2023Article
- Article
- Activation of PI3K/Akt prevents hypoxia/reoxygenation-induced GnRH decline via FOXO3a.Physiological research · 2022Article
- Artificial intelligence framework identifies candidate targets for drug repurposing in Alzheimer's disease.Alzheimer's research & therapy · 2022Article
- Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer's Disease Patients.Cells · 2022Article
- Potential Mechanism Underlying Exercise Upregulated Circulating Blood Exosome miR-215-5p to Prevent Necroptosis of Neuronal Cells and a Model for Early Diagnosis of Alzheimer's Disease.Frontiers in aging neuroscience · 2022Article
- Autophagy and apoptosis cascade: which is more prominent in neuronal death?Cellular and molecular life sciences : CMLS · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Deregulated Cdk5 causes neurotoxic amyloid beta peptide (Aβ) processing and cell death, two hallmarks of Alzheimer's disease, through the Foxo3 transcriptional factor in hippocampal cells, primary neurons and an Alzheimer's disease mouse model. Using an innovative chemical genetic screen, we identified Foxo3 as a direct substrate of Cdk5 in brain lysates. Cdk5 directly phosphorylates Foxo3, which increased its levels and nuclear translocation. Nuclear Foxo3 initially rescued cells from ensuing oxidative stress by upregulating MnSOD (also known as SOD2). However, following prolonged exposure, Foxo3 upregulated Bim (also known as BCL2L11) and FasL (also known as FASLG) causing cell death. Active Foxo3 also increased Aβ(1-42) levels in a phosphorylation-dependent manner. These events were completely inhibited either by expressing phosphorylation-resistant Foxo3 or by depleting Cdk5 or Foxo3, highlighting a key role for Cdk5 in regulating Foxo3. These results were confirmed in an Alzheimer's disease mouse model, which exhibited increased levels and nuclear localization of Foxo3 in hippocampal neurons, which preceded neurodegeneration and Aβ plaque formation, indicating this phenomenon is an early event in Alzheimer's disease pathogenesis. Collectively, these results show that Cdk5-mediated phospho-regulation of Foxo3 can activate several genes that promote neuronal death and aberrant Aβ processing, thereby contributing to the progression of neurodegenerative pathologies.
Indexed as
Identifiers
What OpenQuestion holds
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.