Antibody-bound amyloid precursor protein upregulates ornithine decarboxylase expression

Tatjana Nilsson, Katarzyna Malkiewicz, Maria Gabrielsson, Ronnie Folkesson, Bengt Winblad, Eirikur Benedikz

Publikation: Bidrag til tidsskriftTidsskriftsartikelForskningpeer review

Abstract

Alzheimer's disease is a neurodegenerative disorder characterised by extracellular accumulation of the Abeta peptide, derived from the amyloid precursor protein (APP). The function of APP as a cell surface receptor was examined by ligand-mimicking using an antibody against the APP extracellular domain. Alterations in gene expression evoked by antibody-bound APP were analysed using human pathway-finder gene arrays and the largest change in expression levels was found for ornithine decarboxylase (ODC). These results were confirmed by Western blotting which showed even higher upregulation on the protein level. APP knockdown by RNAi verified that upregulation of ODC was APP-mediated. This APP signalling event did not require gamma-secretase cleavage, as it was independent of the presence of presenilin-1 or -2. The induced ODC expression was rapid and biphasic, resembling growth-factor stimulated signalling events. This study shows that antibody-bound APP leads to altered gene expression that may be relevant to AD.

OriginalsprogEngelsk
TidsskriftBiochemical and Biophysical Research Communications
Vol/bind341
Udgave nummer4
Sider (fra-til)1294-9
Antal sider6
ISSN0006-291X
DOI
StatusUdgivet - 24 mar. 2006
Udgivet eksterntJa

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