Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Alzheimer's disease (AD) is a disorder of two pathologies: amyloid plaques, the core of which is a peptide derived from the amyloid precursor protein (APP), and neurofibrillary tangles composed of highly phosphorylated tau. Protein kinase C (PKC) is known to increase non-amyloidogenic alpha-secretase cleavage of APP, producing secreted APP (sAPPalpha), and glycogen synthase kinase (GSK)-3beta is known to increase tau phosphorylation. Both PKC and GSK-3beta are components of the wnt signaling cascade. Here we demonstrate that overexpression of another member of this pathway, dishevelled (dvl-1), increases sAPPalpha production. The dishevelled action on APP is mediated via both c-jun terminal kinase (JNK) and protein kinase C (PKC)/mitogen-activated protein (MAP) kinase but not via p38 MAP kinase. These data position dvl-1 upstream of both PKC and JNK, thereby explaining the previously observed dual signaling action of dvl-1. Furthermore, we show that human dvl-1 and wnt-1 also reduce the phosphorylation of tau by GSK-3beta. Therefore, both APP metabolism and tau phosphorylation are potentially linked through wnt signaling.


Journal article


J Neurosci

Publication Date





4987 - 4995


Adaptor Proteins, Signal Transducing, Alzheimer Disease, Amyloid Precursor Protein Secretases, Amyloid beta-Protein Precursor, Aspartic Acid Endopeptidases, Calcium-Calmodulin-Dependent Protein Kinases, Cell Line, Dishevelled Proteins, Endopeptidases, Gene Expression, Glycogen Synthase Kinase 3, Glycogen Synthase Kinases, Humans, JNK Mitogen-Activated Protein Kinases, Kidney, Mitogen-Activated Protein Kinases, Mutation, Phosphoproteins, Phosphorylation, Protein Kinase C, Proteins, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Signal Transduction, Transfection, Wnt Proteins, Wnt1 Protein, Zebrafish Proteins, tau Proteins