Induction of Dickkopf-1, a Negative Modulator of the Wnt Pathway, Is Associated with Neuronal Degeneration in Alzheimer's Brain

• DOI: 10.1523/jneurosci.1381-04.2004
• Publication Date: 2004-06-30T16:23:28Z
• Authors: Andrea Caricasole; Agata Copani; Filippo Caraci; Eleonora Aronica; Annemieke J. Roze...; Alessandra Caruso; Marianna Storto; Giovanni Gaviraghi; Georg C. Terstappen; Ferdinando Nicoletti
• Keywords: DKK1; GSK3B; Hyperphosphorylation; Amyloid beta; Tau protein

We used primary cultures of cortical neurons to examine the relationship between beta-amyloid toxicity and hyperphosphorylation tau protein, biochemical substrate for neurofibrillary tangles Alzheimer's brain. Exposure peptide (betaAP) induced expression secreted glycoprotein Dickkopf-1 (DKK1). DKK1 negatively modulates canonical Wnt signaling pathway, thus activating tau-phosphorylating enzyme glycogen synthase kinase-3beta. was at late times after betaAP exposure, its dependent on tumor suppressing protein p53. The antisense knock-down attenuated neuronal apoptosis but nearly abolished increase in phosphorylation betaAP-treated neurons. also expressed by degenerating brain from patients, where it colocalized with distrophic neurites. conclude that induction contributes pathological cascade triggered is critically involved process phosphorylation.