ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Specific inhibition of p25/Cdk5 activity by the Cdk5 inhibitory peptide reduces neurodegeneration in vivo.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 89 citations in OpenAlex.
- Protein Kinases in Alzheimer's Disease: Pioneering Insights into Pathogenesis and Therapeutic Breakthroughs.Current neuropharmacology · 2026Review
- The Duality of Cdk5: A Master Regulator in Neurodevelopment and a Hijacked Oncogene in Cancer.Cells · 2025Review
- Pathological Calcium Signaling in Traumatic Brain Injury and Alzheimer's Disease: From Acute Neuronal Injury to Chronic Neurodegeneration.International journal of molecular sciences · 2025Review
- Impairment of Tricarboxylic Acid Cycle (TCA) Cycle in Alzheimer's Disease: Mechanisms, Implications, and Potential Therapies.Aging and disease · 2025Review
- Tau-targeting nanoparticles for treatment of Alzheimer's disease.Exploration (Beijing, China) · 2025Review
- A Retrospective Tribute to Dr. Harish Pant (1938-2023) and His Seminal Work on Cyclin Dependent Kinase 5.Neurochemical research · 2024Article
- Cyclin-dependent Kinase 5 and Neurodegenerative Diseases.Molecular neurobiology · 2024Review
- Calcium-binding protein 7 expressed in muscle negatively regulates age-related degeneration of neuromuscular junctions in mice.iScience · 2024Article
- Mitigating aberrant Cdk5 activation alleviates mitochondrial defects and motor neuron disease symptoms in spinal muscular atrophy.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- TFP5, a Peptide Derived from Cdk5 Activator p35, Protects Pancreatic β Cells from Glucose Toxicity.Bulletin of experimental biology and medicine · 2023Article
- APPsα rescues CDK5 and GSK3β dysregulation and restores normal spine density in Tau transgenic mice.Frontiers in cellular neuroscience · 2023Article
- Systemic Administration of a Brain Permeable Cdk5 Inhibitor Alters Neurobehavior.Frontiers in pharmacology · 2022Article
- Three decades of Cdk5.Journal of biomedical science · 2021Review
- When Good Kinases Go Rogue: GSK3, p38 MAPK and CDKs as Therapeutic Targets for Alzheimer's and Huntington's Disease.International journal of molecular sciences · 2021Review
- Inhibitors of Cyclin-Dependent Kinases: Types and Their Mechanism of Action.International journal of molecular sciences · 2021Review
- Core cell cycle machinery is crucially involved in both life and death of post-mitotic neurons.Cellular and molecular life sciences : CMLS · 2020Review
- Rapid, quantitative therapeutic screening for Alzheimer's enzymes enabled by optimal signal transduction with transistors.The Analyst · 2020Article
- Metformin Ameliorates Synaptic Defects in a Mouse Model of AD by Inhibiting Cdk5 Activity.Frontiers in cellular neuroscience · 2020Article
- Identification of Quinazolinone Analogs Targeting CDK5 Kinase Activity and Glioblastoma Cell Proliferation.Frontiers in chemistry · 2020Article
- A kinase of many talents: non-neuronal functions of CDK5 in development and disease.Open biology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 6 countries.
Funding
Abstract
The aberrant hyperactivation of Cyclin-dependent kinase 5 (Cdk5), by the production of its truncated activator p25, results in the formation of hyperphosphorylated tau, neuroinflammation, amyloid deposition, and neuronal death in vitro and in vivo. Mechanistically, this occurs as a result of a neurotoxic insult that invokes the intracellular elevation of calcium to activate calpain, which cleaves the Cdk5 activator p35 into p25. It has been shown previously that the p25 transgenic mouse as a model to investigate the mechanistic implications of p25 production in the brain, which recapitulates deregulated Cdk5-mediated neuropathological changes, such as hyperphosphorylated tau and neuronal death. To date, strategies to inhibit Cdk5 activity have not been successful in targeting selectively aberrant activity without affecting normal Cdk5 activity. Here we show that the selective inhibition of p25/Cdk5 hyperactivation in vivo, through overexpression of the Cdk5 inhibitory peptide (CIP), rescues against the neurodegenerative pathologies caused by p25/Cdk5 hyperactivation without affecting normal neurodevelopment afforded by normal p35/Cdk5 activity. Tau and amyloid pathologies as well as neuroinflammation are significantly reduced in the CIP-p25 tetra transgenic mice, whereas brain atrophy and subsequent cognitive decline are reversed in these mice. The findings reported here represent an important breakthrough in elucidating approaches to selectively inhibit the p25/Cdk5 hyperactivation as a potential therapeutic target to reduce neurodegeneration.
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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.