ArticleJournal of neuroinflammation2018
Inhibition of cyclin-dependent kinase 5 affects early neuroinflammatory signalling in murine model of amyloid beta toxicity.
Article in Journal of neuroinflammation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 128 citations in OpenAlex.
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- Protein Kinases in Alzheimer's Disease: Pioneering Insights into Pathogenesis and Therapeutic Breakthroughs.Current neuropharmacology · 2026Review
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- Downregulation of the NF-κB protein p65 is a shared phenotype among most anti-aging interventions.GeroScience · 2025Article
- The Inhibition of Bromodomain and Extraterminal Domain (BET) Proteins Protects Against Microglia-Mediated Neuronal Loss In Vitro.Biomolecules · 2025Article
- The potential link between the development of Alzheimer's disease and osteoporosis.Biogerontology · 2025Review
- Article
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- An Update on Parkinson's Disease and its Neurodegenerative Counterparts.Current medicinal chemistry · 2024Review
- Pre-clinical Aspects and Contemporary Treatments of Parkinson's Disease.CNS & neurological disorders drug targets · 2024Review
- Exploring the role of COX-2 in Alzheimer's disease: Potential therapeutic implications of COX-2 inhibitors.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Review
- The Role of Bromodomain and Extraterminal (BET) Proteins in Controlling the Phagocytic Activity of Microglia In Vitro: Relevance to Alzheimer's Disease.International journal of molecular sciences · 2022Article
- Microbiota-microglia connections in age-related cognition decline.Aging cell · 2022Review
- Effects of estradiol supplementation on the brain transcriptome of old rhesus macaques maintained on an obesogenic diet.GeroScience · 2022Article
- p27, The Cell Cycle and Alzheimer´s Disease.International journal of molecular sciences · 2022Review
- Neuronal cell death mechanisms in Alzheimer's disease: An insight.Frontiers in molecular neuroscience · 2022Review
- The role of Cdk5 in neurological disorders.Frontiers in cellular neuroscience · 2022Review
- Focusing on cyclin-dependent kinases 5: A potential target for neurological disorders.Frontiers in molecular neuroscience · 2022Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundCyclin-dependent kinase 5 (Cdk5) belongs to the family of proline-directed serine/threonine kinases and plays a critical role in neuronal differentiation, migration, synaptogenesis, plasticity, neurotransmission and apoptosis. The deregulation of Cdk5 activity was observed in post mortem analysis of brain tissue of Alzheimer's disease (AD) patients, suggesting the involvement of Cdk5 in the pathomechanism of this neurodegenerative disease. However, our recent study demonstrated the important function of Cdk5 in regulating inflammatory reaction.
methodsSince the role of Cdk5 in regulation of inflammatory signalling in AD is unknown, we investigated the involvement of Cdk5 in neuroinflammation induced by single intracerebroventricular (icv) injection of amyloid beta protein (Aβ) oligomers in mouse. The brain tissue was analysed up to 35 days post injection. Roscovitine (intraperitoneal administration) was used as a potent Cdk5 inhibitor. The experiments were also performed on human neuroblastoma SH-SY5Y as well as mouse BV2 cell lines treated with exogenous oligomeric Aβ.
resultsOur results demonstrated that single injection of Aβ oligomers induces long-lasting activation of microglia and astrocytes in the hippocampus. We observed also profound, early inflammatory response in the mice hippocampus, leading to the significant elevation of pro-inflammatory cytokines expression (e.g. TNF-α, IL-1β, IL-6). Moreover, Aβ oligomers elevated the formation of truncated protein p25 in mouse hippocampus and induced overactivation of Cdk5 in neuronal cells. Importantly, administration of roscovitine reduced the inflammatory processes evoked by Aβ in the hippocampus, leading to the significant decrease of cytokines level.
conclusionsThese studies clearly show the involvement of Cdk5 in modulation of brain inflammatory response induced by Aβ and may indicate this kinase as a novel target for pharmacological intervention in AD.
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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.