Glucocorticoids trigger Alzheimer disease-like pathobiochemistry in rat neuronal cells expressing human tau

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dc.contributor.authorSotiropoulos, I.en
dc.contributor.authorCatania, C.en
dc.contributor.authorRiedemann, T.en
dc.contributor.authorFry, J. P.en
dc.contributor.authorBreen, K. C.en
dc.contributor.authorMichaelidis, T. M.en
dc.contributor.authorAlmeida, O. F. X.en
dc.date.accessioned2015-11-24T16:34:07Z
dc.date.available2015-11-24T16:34:07Z
dc.identifier.issn0022-3042-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/7759
dc.rightsDefault Licence-
dc.subjectalzheimer's diseaseen
dc.subjectamyloid precursor proteinen
dc.subjectglucocorticoidsen
dc.subjectpc12 cellsen
dc.subjectrat neuronsen
dc.subjecttauen
dc.subjectamyloid precursor proteinen
dc.subjectglycogen-synthase kinase-3-betaen
dc.subjecttransgenic miceen
dc.subjectin-vivoen
dc.subjecthyperphosphorylated-tauen
dc.subjectinduced neurotoxicityen
dc.subjecthippocampal atrophyen
dc.subjectoxien
dc.titleGlucocorticoids trigger Alzheimer disease-like pathobiochemistry in rat neuronal cells expressing human tauen
heal.abstractAmyloid precursor protein (APP) mis-processing and aberrant tau hyperphosphorylation are causally related to the pathogenesis and neurodegenerative processes that characterize Alzheimer's disease (AD). Abnormal APP metabolism leads to the generation of neurotoxic amyloid beta (Ab), whereas tau hyperphosphorylation culminates in cytoskeletal disturbances, neuronal dysfunction and death. Many AD patients hypersecrete glucocorticoids (GC) while neuronal structure, function and survival are adversely influenced by elevated GC levels. We report here that a rat neuronal cell line (PC12) engineered to express the human ortholog of the tau protein (PC12-htau) becomes more vulnerable to the toxic effects of either Ab or GC treatment. Importantly, APP metabolism in GC-treated PC12-htau cells is selectively shifted towards increased production of the pro-amyloidogenic peptide C99. Further, GC treatment results in hyperphosphorylation of human tau at AD-relevant sites, through the cyclin-dependent kinase 5 (E. C. 2.7.11.26) and GSK3 (E. C. 2.7.11.22) protein kinases. Pulse-chase experiments revealed that GC treatment increased the stability of tau protein rather than its de novo synthesis. GC treatment also induced accumulation of transiently expressed EGFP-tau in the neuronal perikarya. Together with previous evidence showing that Ab can activate cyclin-dependent kinase 5 and GSK3, these results uncover a potential mechanism through which GC may contribute to AD neuropathology.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primaryDOI 10.1111/j.1471-4159.2008.05613.x-
heal.identifier.secondary<Go to ISI>://000259949900008-
heal.identifier.secondaryhttp://onlinelibrary.wiley.com/store/10.1111/j.1471-4159.2008.05613.x/asset/j.1471-4159.2008.05613.x.pdf?v=1&t=h279w0a2&s=e19943671f4cc29aad88a942da42eb4f3f851e59-
heal.journalNameJ Neurochemen
heal.journalTypepeer reviewed-
heal.languageen-
heal.publicationDate2008-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών και Τεχνολογιών. Τμήμα Βιολογικών Εφαρμογών και Τεχνολογιώνel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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