ArticleProceedings of the National Academy of Sciences of the United States of America2023
A Cdk5-derived peptide inhibits Cdk5/p25 activity and improves neurodegenerative phenotypes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 50 citations in OpenAlex.
- The FGD5-AS1/miR-142-5p/CDK5 axis promotes ESCC progression by regulating mitochondrial fission and mitophagy: insights from integrative bioinformatics and experimental analyses.World journal of surgical oncology · 2026Article
- Beyond microtubule regulation: the multifaceted roles of tau in neuronal function and dysfunction.Translational psychiatry · 2026Review
- Brain peptides in Alzheimer's disease - pathophysiology and therapeutic advances.Cell and tissue research · 2026Review
- A patent review of cyclin-dependent kinase 5 (CDK5) inhibitors (1999-2025).Frontiers in bioengineering and biotechnology · 2026Review
- Advances in the treatment of Alzheimer's disease.Frontiers in pharmacology · 2026Review
- Brain region-specific dopamine receptor changes and astrocyte activation influence tau pathology through CDK5 in Alzheimer's disease models.Journal of Alzheimer's disease : JAD · 2025Article
- Aggregation Characteristics of Tau Phosphorylated by Various Kinases as Observed by Quantum Dot Fluorescence Imaging.International journal of molecular sciences · 2025Article
- Targeting a Tau Kinase Cdk5, Cyclin-Dependent Kinase: A Blood-Based Diagnostic Marker and Therapeutic Earmark for Alzheimer's Disease.Biomolecules · 2025Article
- CDK5-mediated hyperphosphorylation of Tau217 impairs neuronal synaptic structure and exacerbates cognitive impairment in Alzheimer's disease.Translational psychiatry · 2025Article
- CDK5 Inhibits Synphilin-1 Ubiquitination and Basal Mitophagy: Implications for Parkinson's Disease.International journal of molecular sciences · 2025Article
- Polycyclitol Derivatives Restore Long- Term Memory Via cdk5/p25 Activation of Tau Signaling in Experimental Cerebral Malaria.Neurochemical research · 2025Article
- Reln-Dab1 pathway mitigates retinal ganglion cell apoptosis in retinal ischemia-reperfusion injury.Cell death & disease · 2025Article
- Development of a brain-penetrant G9a methylase inhibitor to target Alzheimer's disease-associated proteopathology.Nature communications · 2025Article
- Article
- Physiological and pathological roles of the transcriptional kinases CDK12 and CDK13 in the central nervous system.Cell death and differentiation · 2025Review
- Peptide Biomarkers - An Emerging Diagnostic Tool and Current Applicable Assay.Current protein & peptide science · 2025Review
- CDK5 Deficiency Does not Impair Neuronal Differentiation of Human Induced Pluripotent Stem Cells but Affects Neurite Outgrowth.Molecular neurobiology · 2025Article
- Sigma receptors and mitochondria-associated ER membranes are converging therapeutic targets for Alzheimer's disease.Frontiers in neuroscience · 2025Review
- Cyclin-dependent Kinase 5 and Neurodegenerative Diseases.Molecular neurobiology · 2024Review
- Unveiling Potential Neurotoxic Mechansisms: Pb-Induced Activation of CDK5-p25 Signaling Axis in Alzheimer's Disease Development, Emphasizing CDK5 Inhibition and Formation of Toxic p25 Species.Molecular neurobiology · 2024Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
Abstract
Aberrant activity of cyclin-dependent kinase (Cdk5) has been implicated in various neurodegenerative diseases. This deleterious effect is mediated by pathological cleavage of the Cdk5 activator p35 into the truncated product p25, leading to prolonged Cdk5 activation and altered substrate specificity. Elevated p25 levels have been reported in humans and rodents with neurodegeneration, and the benefit of genetically blocking p25 production has been demonstrated previously in rodent and human neurodegenerative models. Here, we report a 12-amino-acid-long peptide fragment derived from Cdk5 (Cdk5i) that is considerably smaller than existing peptide inhibitors of Cdk5 (P5 and CIP) but shows high binding affinity toward the Cdk5/p25 complex, disrupts the interaction of Cdk5 with p25, and lowers Cdk5/p25 kinase activity. When tagged with a fluorophore (FITC) and the cell-penetrating transactivator of transcription (TAT) sequence, the Cdk5i-FT peptide exhibits cell- and brain-penetrant properties and confers protection against neurodegenerative phenotypes associated with Cdk5 hyperactivity in cell and mouse models of neurodegeneration, highlighting Cdk5i's therapeutic potential.
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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.