ArticleJournal of cell science2017
The Cdk5-Mcl-1 axis promotes mitochondrial dysfunction and neurodegeneration in a model of Alzheimer's disease.
Article in Journal of cell science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Stabilization of cyclin D3 protein by CDKN1A (p21Cell communication and signaling : CCS · 2026Article
- Mitotic errors as triggers of cell death and inflammation.Nature cell biology · 2026Review
- Targeting a Tau Kinase Cdk5, Cyclin-Dependent Kinase: A Blood-Based Diagnostic Marker and Therapeutic Earmark for Alzheimer's Disease.Biomolecules · 2025Article
- CDK5: Insights into its roles in diseases.Molecular biology reports · 2025Review
- Receptor-mediated mitophagy: a new target of neurodegenerative diseases.Frontiers in neurology · 2025Review
- Cyclin-dependent Kinase 5 and Neurodegenerative Diseases.Molecular neurobiology · 2024Review
- CDK5: an oncogene or an anti-oncogene: location location location.Molecular cancer · 2023Review
- PINK1 overexpression prevents forskolin-induced tau hyperphosphorylation and oxidative stress in a rat model of Alzheimer's disease.Acta pharmacologica Sinica · 2022Article
- Article
- Skp2 stabilizes Mcl-1 and confers radioresistance in colorectal cancer.Cell death & disease · 2022Article
- Focusing on cyclin-dependent kinases 5: A potential target for neurological disorders.Frontiers in molecular neuroscience · 2022Review
- The regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer's disease.Acta materia medica · 2022Article
- The role of Cdk5 in neurological disorders.Frontiers in cellular neuroscience · 2022Review
- The role of Bcl-2 proteins in modulating neuronal CaBiochimica et biophysica acta. Molecular cell research · 2021Review
- Identification of differentially expressed microRNAs and their target genes in the hippocampal tissues of Fmr1 knockout mice.American journal of translational research · 2020Article
- Site-specific phosphorylation of Fbxw7 by Cdk5/p25 and its resulting decreased stability are linked to glutamate-induced excitotoxicity.Cell death & disease · 2019Article
- Identification of LIMK2 as a therapeutic target in castration resistant prostate cancer.Cancer letters · 2019Article
- Multifaceted Regulation of ALDH1A1 by Cdk5 in Alzheimer's Disease Pathogenesis.Molecular neurobiology · 2019Article
- Comparing effects of CDK inhibition and E2F1/2 ablation on neuronal cell death pathways in vitro and after traumatic brain injury.Cell death & disease · 2018Article
- Inactivation of Cyclin-Dependent Kinase 5 in Hair Cells Causes Hearing Loss in Mice.Frontiers in molecular neuroscience · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Cdk5 deregulation is highly neurotoxic in Alzheimer's disease (AD). We identified Mcl-1 as a direct Cdk5 substrate using an innovative chemical screen in mouse brain lysates. Our data demonstrate that Mcl-1 levels determine the threshold for cellular damage in response to neurotoxic insults. Mcl-1 is a disease-specific target of Cdk5, which associates with Cdk5 under basal conditions, but is not regulated by it. Neurotoxic insults hyperactivate Cdk5 causing Mcl-1 phosphorylation at T92. This phosphorylation event triggers Mcl-1 ubiquitylation, which directly correlates with mitochondrial dysfunction. Consequently, ectopic expression of phosphorylation-dead T92A-Mcl-1 fully prevents mitochondrial damage and subsequent cell death triggered by neurotoxic treatments in neuronal cells and primary cortical neurons. Notably, enhancing Mcl-1 levels offers comparable neuroprotection to that observed upon Cdk5 depletion, suggesting that Mcl-1 degradation by direct phosphorylation is a key mechanism by which Cdk5 promotes neurotoxicity in AD. The clinical significance of the Mcl-1-Cdk5 axis was investigated in human AD clinical specimens, revealing an inverse correlation between Mcl-1 levels and disease severity. These results emphasize the potential of Mcl-1 upregulation as an attractive therapeutic strategy for delaying or preventing neurodegeneration in 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.