%0 Journal Article %A A. Mudher %A S. Chapman %A J. Richardson %A A. Asuni %A G. Gibb %A C. Pollard %A R. Killick %A T. Iqbal %A L. Raymond %A I. Varndell %A P. Sheppard %A A. Makoff %A E. Gower %A P. E. Soden %A P. Lewis %A M. Murphy %A T. E. Golde %A H. T. Rupniak %A B. H. Anderton %A S. Lovestone %T Dishevelled Regulates the Metabolism of Amyloid Precursor Protein via Protein Kinase C/Mitogen-Activated Protein Kinase and c-Jun Terminal Kinase %D 2001 %R 10.1523/JNEUROSCI.21-14-04987.2001 %J The Journal of Neuroscience %P 4987-4995 %V 21 %N 14 %X 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 α-secretase cleavage of APP, producing secreted APP (sAPPα), and glycogen synthase kinase (GSK)-3β is known to increase tau phosphorylation. Both PKC and GSK-3β are components of the wnt signaling cascade. Here we demonstrate that overexpression of another member of this pathway, dishevelled (dvl-1), increases sAPPα 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-3β. Therefore, both APP metabolism and tau phosphorylation are potentially linked through wnt signaling. %U https://www.jneurosci.org/content/jneuro/21/14/4987.full.pdf