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Inhibition of cyclin-dependent kinase 5 affects early neuroinflammatory signalling in murine model of amyloid beta toxicity

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cris.lastimport.scopus2024-02-12T19:40:21Z
dc.abstract.enBackground: Cyclin-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. Methods: Since 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 (A beta) 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 A beta. Results: Our results demonstrated that single injection of A beta 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-alpha, IL-1 beta, IL-6). Moreover, A beta 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 A beta in the hippocampus, leading to the significant decrease of cytokines level. Conclusions: These studies clearly show the involvement of Cdk5 in modulation of brain inflammatory response induced by A beta and may indicate this kinase as a novel target for pharmacological intervention in AD.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorGąssowska-Dobrowolska, Magdalena
dc.contributor.authorStrawski, Marcin
dc.contributor.authorWilkaniec, Anna
dc.contributor.authorAdamczyk, Agata
dc.contributor.authorCzapski, Grzegorz
dc.date.accessioned2024-01-25T04:14:41Z
dc.date.available2024-01-25T04:14:41Z
dc.date.copyright2018-01-04
dc.date.issued2018
dc.description.accesstimeAT_PUBLICATION
dc.description.financeNie dotyczy
dc.description.number1
dc.description.versionFINAL_PUBLISHED
dc.description.volume15
dc.identifier.doi10.1186/S12974-017-1027-Y
dc.identifier.issn1742-2094
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/109314
dc.identifier.weblinkhttps://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-017-1027-y
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofJournal of Neuroinflammation
dc.relation.pagesart.no. 1
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.enNeuroinflammation
dc.subject.enAmyloid beta
dc.subject.enAlzheimer's disease
dc.subject.enCdk5
dc.subject.enCytokines
dc.subject.enGene expression
dc.titleInhibition of cyclin-dependent kinase 5 affects early neuroinflammatory signalling in murine model of amyloid beta toxicity
dc.typeJournalArticle
dspace.entity.typePublication