ArticleCell death & disease2018
Zinc induces CDK5 activation and neuronal death through CDK5-Tyr15 phosphorylation in ischemic stroke.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 38 citations in OpenAlex.
- Iron, Copper, and Zinc Dyshomeostasis in Cardiovascular and Cerebrovascular Diseases: Redox Mechanisms, Evidence Levels, and Translational Prospects.International journal of molecular sciences · 2026Review
- Zinc homeostasis imbalance: Potential therapeutic value in neurodegenerative diseases.Neural regeneration research · 2026Article
- Repurposing trazodone for Alzheimer's disease to modulate soluble ST2 levels and alleviate Alzheimer's pathology.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Nanoscale CabioRxiv : the preprint server for biology · 2026Article
- Metal ion dyshomeostasis in neurological disorders: from pathological mechanisms to targeted neuroprotective and regenerative strategies.Frontiers in pharmacology · 2026Review
- Potentiating microglial efferocytosis by MFG-E8 improves survival and neurological outcome after successful cardiopulmonary resuscitation in mice.Brain pathology (Zurich, Switzerland) · 2025Article
- Antioxidant Effect of Naringin Demonstrated Through a Bayes' Theorem Driven Multidisciplinary Approach Reveals its Prophylactic Potential as a Dietary Supplement for Ischemic Stroke.Molecular neurobiology · 2025Article
- Role of Tau Protein in Neurodegenerative Diseases and Development of Its Targeted Drugs: A Literature Review.Molecules (Basel, Switzerland) · 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
- Inhibition of hippocampal cyclin-dependent kinase 5 activity ameliorates learning and memory dysfunction in a mouse model of bronchopulmonary dysplasia.CNS neuroscience & therapeutics · 2023Article
- The Important Role of Zinc in Neurological Diseases.Biomolecules · 2022Review
- Zinc in Regulating Protein Kinases and Phosphatases in Neurodegenerative Diseases.Biomolecules · 2022Review
- The LPA-CDK5-tau pathway mediates neuronal injury in an in vitro model of ischemia-reperfusion insult.BMC neurology · 2022Article
- Kai-Xin-San Inhibits Tau Pathology and Neuronal Apoptosis in Aged SAMP8 Mice.Molecular neurobiology · 2022Article
- Thrombin induces ACSL4-dependent ferroptosis during cerebral ischemia/reperfusion.Signal transduction and targeted therapy · 2022Article
- Role of cyclin-dependent kinase 5 in early brain injury following experimental subarachnoid hemorrhage.Experimental and therapeutic medicine · 2022Article
- The role of Cdk5 in neurological disorders.Frontiers in cellular neuroscience · 2022Review
- Rodent Models of Vascular Cognitive Impairment.Journal of molecular neuroscience : MN · 2021Review
- Review
- Repurposing antimycotic ciclopirox olamine as a promising anti-ischemic stroke agent.Acta pharmaceutica Sinica. B · 2020Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CDK5 activation promotes ischemic neuronal death in stroke, with the recognized activation mechanism being calpain-dependent p35 cleavage to p25. Here we reported that CDK5-Tyr15 phosphorylation by zinc induced CDK5 activation in brain ischemic injury. CDK5 activation and CDK5-Tyr15 phosphorylation were observed in the hippocampus of the rats that had been subjected to middle cerebral artery occlusion, both of which were reversed by pretreatment with zinc chelator; while p35 cleavage and calpain activation in ischemia were not reversed. Zinc incubation resulted in CDK5-Tyr15 phosphorylation and CDK5 activation, without increasing p35 cleavage in cultured cells. Site mutation experiment confirmed that zinc-induced CDK5 activation was dependent on Tyr15 phosphorylation. Further exploration showed that Src kinase contributed to zinc-induced Tyr15 phosphorylation and CDK5 activation. Src kinase inhibition or expression of an unphosphorylable mutant Y15F-CDK5 abolished Tyr15 phosphorylation, prevented CDK5 activation and protected hippocampal neurons from ischemic insult in rats. We conclude that zinc-induced CDK5-Tyr15 phosphorylation underlies CDK5 activation and promotes ischemic neuronal death in stroke.
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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.