Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/8398
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dc.contributor.authorResende, Rosa-
dc.contributor.authorFerreiro, Elisabete-
dc.contributor.authorPereira, Cláudia-
dc.contributor.authorOliveira, Catarina Resende-
dc.date.accessioned2009-02-09T14:53:37Z-
dc.date.available2009-02-09T14:53:37Z-
dc.date.issued2008en_US
dc.identifier.citationJournal of Neuroscience Research. 86:9 (2008) 2091-2099en_US
dc.identifier.urihttp://hdl.handle.net/10316/8398-
dc.description.abstractIntracellular neurofibrillary tangles, one of the characteristic hallmarks of Alzheimer's disease (AD), are mainly composed of hyperphosphorylated tau. The abnormal tau phosphorylation seems to be related to altered activity of kinases such as glycogen synthase kinase-3beta (GSK-3beta). Tau pathology is thought to be a later event during the progression of the disease, and it seems to occur as a consequence of amyloid-beta (Abeta) peptide accumulation. The aim of this work was to investigate whether soluble Abeta1-42, particularly oligomers that correspond to the neurotoxic species involved early in the development of AD, triggers tau phosphorylation by a mechanism involving activation of tau-kinase GSK-3beta. Several studies suggest that GSK-3beta plays a central role in signaling the downstream effects of endoplasmic reticulum (ER) stress. Therefore, the involvement of ER Ca2+ release in GSK-3beta activation and tau phosphorylation induced by Abeta1-42 oligomers was evaluated using dantrolene, an inhibitor of Ca2+ release through channels associated with ER ryanodine receptors. We observed that Abeta1-42 oligomers increase tau phosphorylation and compromises cell survival through a mechanism mediated by GSK-3beta activation. We also demonstrated that oligomeric Abeta1-42 induces ER stress and that ER Ca2+ release is involved in oligomer-induced GSK-3beta activation and tau phosphorylation. This work suggests that GSK-3beta can be a promising target for therapeutic intervention in AD. © 2008 Wiley-Liss, Inc.en_US
dc.language.isoengeng
dc.rightsopenAccesseng
dc.titleER stress is involved in Abeta-induced GSK-3beta activation and tau phosphorylationen_US
dc.typearticleen_US
dc.identifier.doi10.1002/jnr.21648en_US
item.languageiso639-1en-
item.fulltextCom Texto completo-
item.grantfulltextopen-
crisitem.author.researchunitCNC.IBILI-
crisitem.author.orcid0000-0002-0504-5756-
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
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