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Title: Destabilization of beta-catenin by mutations in presenilin-1 potentiates neuronal apoptosis
Authors: Zhang, Z ×
Hartmann, H
Do, V M
Abramowski, D
Sturchler-Pierrat, C
Staufenbiel, M
Sommer, B
van de Wetering, M
Clevers, H
Saftig, P
De Strooper, Bart
He, X
Yankner, B A #
Issue Date: Nov-1998
Series Title: Nature vol:395 issue:6703 pages:698-702
Abstract: Mutations of the presenilin-1 gene are a major cause of familial early-onset Alzheimer's disease. Presenilin-1 can associate with members of the catenin family of signalling proteins, but the significance of this association is unknown. Here we show that presenilin-1 forms a complex with beta-catenin in vivo that increases beta-catenin stability. Pathogenic mutations in the presenilin-1 gene reduce the ability of presenilin-1 to stabilize beta-catenin, and lead to increased degradation of beta-catenin in the brains of transgenic mice. Moreover, beta-catenin levels are markedly reduced in the brains of Alzheimer's disease patients with presenilin-1 mutations. Loss of beta-catenin signalling increases neuronal vulnerability to apoptosis induced by amyloid-beta protein. Thus, mutations in presenilin-1 may increase neuronal apoptosis by altering the stability of beta-catenin, predisposing individuals to early-onset Alzheimer's disease.
ISSN: 0028-0836
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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