ArticleMolecular biology of the cell2007
Cdk5 Modulation of mitogen-activated protein kinase signaling regulates neuronal survival.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 75 citations in OpenAlex.
- Exploring New Structures of Kinase Inhibitors and Multitarget Strategies in Alzheimer's Disease Treatment.Protein and peptide letters · 2025Review
- A Retrospective Tribute to Dr. Harish Pant (1938-2023) and His Seminal Work on Cyclin Dependent Kinase 5.Neurochemical research · 2024Article
- Neurodegeneration and convergent factors contributing to the deterioration of the cytoskeleton in Alzheimer's disease, cerebral ischemia and multiple sclerosis (Review).Biomedical reports · 2022Review
- Playing the Whack-A-Mole Game: ERK5 Activation Emerges Among the Resistance Mechanisms to RAF-MEK1/2-ERK1/2- Targeted Therapy.Frontiers in cell and developmental biology · 2021Review
- RPS23RG1 modulates tau phosphorylation and axon outgrowth through regulating p35 proteasomal degradation.Cell death and differentiation · 2021Article
- Altered expression of the Cdk5 activator-like protein, Cdk5α, causes neurodegeneration, in part by accelerating the rate of aging.Disease models & mechanisms · 2018Article
- CDK5-dependent activation of dynein in the axon initial segment regulates polarized cargo transport in neurons.Traffic (Copenhagen, Denmark) · 2017Article
- The O-GlcNAc Modification of CDK5 Involved in Neuronal Apoptosis Following In Vitro Intracerebral Hemorrhage.Cellular and molecular neurobiology · 2017Article
- Article
- CDK5 downregulation enhances synaptic plasticity.Cellular and molecular life sciences : CMLS · 2017Article
- TFP5/TP5 peptide provides neuroprotection in the MPTP model of Parkinson's disease.Neural regeneration research · 2016Review
- Enhancement of Peripheral Nerve Regrowth by the Purine Nucleoside Analog and Cell Cycle Inhibitor, Roscovitine.Frontiers in cellular neuroscience · 2016Article
- Astrocyte NMDA receptors' activity sustains neuronal survival through a Cdk5-Nrf2 pathway.Cell death and differentiation · 2015Article
- Cyclin-dependent kinase 5 activates guanine nucleotide exchange factor GIV/Girdin to orchestrate migration-proliferation dichotomy.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
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- p35 and Rac1 underlie the neuroprotection and cognitive improvement induced by CDK5 silencing.Journal of neurochemistry · 2015Article
- Sigma-1 receptor regulates Tau phosphorylation and axon extension by shaping p35 turnover via myristic acid.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Korean Red Ginseng protects dopaminergic neurons by suppressing the cleavage of p35 to p25 in a Parkinson's disease mouse model.Journal of ginseng research · 2015Article
- Divergent and convergent roles for kinases and phosphatases in neurofilament dynamics.Journal of cell science · 2014Article
- Derailed intraneuronal signalling drives pathogenesis in sporadic and familial Alzheimer's disease.BioMed research international · 2014Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Cdk5, a cyclin-dependent kinase, is critical for neuronal development, neuronal migration, cortical lamination, and survival. Its survival role is based, in part, on "cross-talk" interactions with apoptotic and survival signaling pathways. Previously, we showed that Cdk5 phosphorylation of mitogen-activated protein kinase kinase (MEK)1 inhibits transient activation induced by nerve growth factor (NGF) in PC12 cells. To further explore the nature of this inhibition, we studied the kinetics of NGF activation of extracellular signal-regulated kinase (Erk)1/2 in cortical neurons with or without roscovitine, an inhibitor of Cdk5. NGF alone induced an Erk1/2-transient activation that peaked in 15 min and declined rapidly to baseline. Roscovitine, alone or with NGF, reached peak Erk1/2 activation in 30 min that was sustained for 48 h. Moreover, the sustained Erk1/2 activation induced apoptosis in cortical neurons. Significantly, pharmacological application of the MEK1 inhibitor PD98095 to roscovitine-treated cortical neurons prevented apoptosis. These results were also confirmed by knocking down Cdk5 activity in cortical neurons with Cdk5 small interference RNA. Apoptosis was correlated with a significant shift of phosphorylated tau and neurofilaments from axons to neuronal cell bodies. These results suggest that survival of cortical neurons is also dependent on tight Cdk5 modulation of the mitogen-activated protein kinase signaling pathway.
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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.