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Antibody-bound amyloid precursor protein upregulates ornithine decarboxylase expression.

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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Nilsson T,Malkiewicz K,Gabrielsson M,Folkesson R,Winblad B,Benedikz E

doi

10.1016/j.bbrc.2006.01.096

subject

Has Abstract

pub_date

2006-03-24 00:00:00

pages

1294-9

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(06)00189-6

journal_volume

341

pub_type

杂志文章

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