http://www.cnr.it/ontology/cnr/individuo/prodotto/ID26955
Increased Dickkopf-1 expression in transgenic mouse models of neurodegenerative disease (Articolo in rivista)
- Type
- Label
- Increased Dickkopf-1 expression in transgenic mouse models of neurodegenerative disease (Articolo in rivista) (literal)
- Anno
- 2010-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1111/j.1471-4159.2009.06566.x (literal)
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- Rosi M.C.; Luccarini I.; Grossi C.; Fiorentini A.; Spillantini M.G.; Prisco A.; Scali C.; Gianfriddo M.; Caricasole A.; Terstappen G.C.; Casamenti F. (literal)
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- Department of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy
Department of Clinical Neurosciences, Brain Repair Centre, University of Cambridge, Cambridge, UK
Istituto di Genetica e Biofisica \"A. Buzzati Traverso\", CNR, Napoli, Italy
Siena Biotech S.p.A., Siena, Italy (literal)
- Titolo
- Increased Dickkopf-1 expression in transgenic mouse models of neurodegenerative disease (literal)
- Abstract
- To investigate the role of the Wnt inhibitor Dickkopf-1 (DKK-1) in the pathophysiology of neurodegenerative diseases, we analysed DKK-1 expression and localization in transgenic mouse models expressing familial Alzheimer's disease mutations and a frontotemporal dementia mutation. A significant increase of DKK-1 expression was found in the diseased brain areas of all transgenic lines, where it co-localized with hyperphosphorylated tau-bearing neurons. In TgCRND8 mice, DKK-1 immunoreactivity was detected in neurons surrounding amyloid deposits and within the choline acetyltransferase-positive neurons of the basal forebrain. Active glycogen synthase kinase-3 (GSK-3) was found to co-localize with DKK-1 and phospho-tau staining. Downstream to GSK-3, a significant reduction in beta-catenin translocation to the nucleus, indicative of impaired Wnt signaling functions, was found as well. Cumulatively, our findings indicate that DKK-1 expression is associated with events that lead to neuronal death in neurodegenerative diseases and support a role for DKK-1 as a key mediator of neurodegeneration with therapeutic potential (literal)
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