Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/8499
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dc.contributor.authorLopes, João-
dc.contributor.authorOliveira, Catarina-
dc.contributor.authorAgostinho, Paula-
dc.date.accessioned2009-02-17T10:51:29Z-
dc.date.available2009-02-17T10:51:29Z-
dc.date.issued2007en_US
dc.identifier.citationCellular and Molecular Neurobiology. 27:7 (2007) 943-957en_US
dc.identifier.urihttp://hdl.handle.net/10316/8499-
dc.description.abstractAbstract Tau hyperphosphorylation, amyloid plaques, and neuronal death are major neuropathological features of Alzheimer’s disease (AD) and Prion-related encephalopathies (PRE). Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase, active in post-mitotic neurons, where it regulates survival and death pathways. Overactivation of Cdk5 is conferred by p25, a truncated fragment of the p35 activator formed upon calpain activation. Cdk5 deregulation causes abnormal phosphorylation of microtubule-associated protein tau, leading to neurodegeneration. In this work we investigated the involvement of Cdk5 in the neurodegeneration triggered by amyloid-beta (Aß) and prion (PrP) peptides, the culprit agents of AD and PRE. As a work model, we used cultured rat cortical neurons treated with Aß1–40 and PrP106–126 synthetic peptides. The obtained data show that apoptotic neuronal death caused by both the peptides was in part due to Cdk5 deregulation. After peptide treatment, p25 levels were significantly enhanced in a pattern consistent with the augment in calpain activity. Moreover, Aß1–40 and PrP106–126 increased the levels of tau protein phosphorylated at Ser202/Thr205. Cdk5 (roscovitine) and calpain (MDL28170) inhibitors reverted tau hyperphosphorylation and prevented neuronal death caused by Aß1–40 and PrP106–126. This study demonstrates, for the first time, that Cdk5 is involved in PrP-neurotoxicity. Altogether, our data suggests that Cdk5 plays an active role in the pathogenesis of AD and PRE.en_US
dc.language.isoengeng
dc.rightsopenAccesseng
dc.titleRole of Cyclin-Dependent Kinase 5 in the Neurodegenerative Process Triggered by Amyloid-Beta and Prion Peptides: Implications for Alzheimer’s Disease and Prion-Related Encephalopathiesen_US
dc.typearticleen_US
dc.identifier.doi10.1007/s10571-007-9224-3en_US
uc.controloAutoridadeSim-
item.fulltextCom Texto completo-
item.languageiso639-1en-
item.grantfulltextopen-
crisitem.author.researchunitCNC.IBILI-
crisitem.author.researchunitCNC.IBILI-
crisitem.author.orcid0000-0002-5122-1802-
crisitem.author.orcid0000-0001-5523-4945-
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
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