ArticlePloS one2013
Efficacy of cyclin dependent kinase 4 inhibitors as potent neuroprotective agents against insults relevant to Alzheimer's disease.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- The Pschorr Reaction: Recent Advances and Application in Heterocyclic Synthesis.Molecules (Basel, Switzerland) · 2026Review
- Cyclin-dependent kinases: Masters of the eukaryotic universe.Wiley interdisciplinary reviews. RNA · 2023Review
- Melatonin as a Harmonizing Factor of Circadian Rhythms, Neuronal Cell Cycle and Neurogenesis: Additional Arguments for Its Therapeutic Use in Alzheimer's Disease.Current neuropharmacology · 2023Review
- Identification of Novel Kinases of Tau Using Fluorescence Complementation Mass Spectrometry (FCMS).Molecular & cellular proteomics : MCP · 2022Article
- Protocols for Characterization of Cdk5 Kinase Activity.Current protocols · 2021Article
- Tau and DNA Damage in Neurodegeneration.Brain sciences · 2020Review
- CDK4 and CDK5 Inhibition Have Comparable Mild Hypothermia Effects in Preventing Drp1-Dependent Mitochondrial Fission and Neuron Death Induced by MPPMolecular neurobiology · 2020Article
- Rational drug design, synthesis, and biological evaluation of novel chiral tetrahydronaphthalene-fused spirooxindole as MDM2-CDK4 dual inhibitor against glioblastoma.Acta pharmaceutica Sinica. B · 2020Article
- Cell Cycle Deficits in Neurodegenerative Disorders: Uncovering Molecular Mechanisms to Drive Innovative Therapeutic Development.Aging and disease · 2020Review
- HDAC1 dysregulation induces aberrant cell cycle and DNA damage in progress of TDP-43 proteinopathies.EMBO molecular medicine · 2020Article
- Article
- Aberrant Neuronal Cell Cycle Re-Entry: The Pathological Confluence of Alzheimer's Disease and Brain Insulin Resistance, and Its Relation to Cancer.Journal of Alzheimer's disease : JAD · 2019Review
- Reduced brain insulin signaling: A seminal process in Alzheimer's disease pathogenesis.Neuropharmacology · 2018Review
- Marine-derived protein kinase inhibitors for neuroinflammatory diseases.Biomedical engineering online · 2018Review
- Cell cycle inhibition reduces inflammatory responses, neuronal loss, and cognitive deficits induced by hypobaria exposure following traumatic brain injury.Journal of neuroinflammation · 2016Article
- Binding interaction of a gamma-aminobutyric acid derivative with serum albumin: an insight by fluorescence and molecular modeling analysis.SpringerPlus · 2016Article
- Regulation of Bim in Health and Disease.Oncotarget · 2015Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease with no cure till today. Aberrant activation of cell cycle regulatory proteins is implicated in neurodegenerative diseases including AD. We and others have shown that Cyclin dependent kinase 4 (Cdk4) is activated in AD brain and is required for neuron death. In this study, we tested the efficiency of commercially available Cdk4 specific inhibitors as well as a small library of synthetic molecule inhibitors targeting Cdk4 as neuroprotective agents in cellular models of neuron death. We found that several of these inhibitors significantly protected neuronal cells against death induced by nerve growth factor (NGF) deprivation and oligomeric beta amyloid (Aβ) that are implicated in AD. These neuroprotective agents inhibit specifically Cdk4 kinase activity, loss of mitochondrial integrity, induction of pro-apoptotic protein Bim and caspase3 activation in response to NGF deprivation. The efficacies of commercial and synthesized inhibitors are comparable. The synthesized molecules are either phenanthrene based or naphthalene based and they are synthesized by using Pschorr reaction and Buchwald coupling respectively as one of the key steps. A number of molecules of both kinds block neurodegeneration effectively. Therefore, we propose that Cdk4 inhibition would be a therapeutic choice for ameliorating neurodegeneration in AD and these synthetic Cdk4 inhibitors could lead to development of effective drugs for 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.