O-GlcNAcylation increases non-amyloidogenic processing of the amyloid-β precursor protein (APP)

Jacobsen, Kristin T.; Iverfeldt, Kerstin

O-GlcNAcylation increases non-amyloidogenic processing of the amyloid-β precursor protein (APP)

2011

Jacobsen, Kristin T. | Iverfeldt, Kerstin

The amyloid-β precursor protein (APP) was shown to be O-GlcNAcylated 15years ago, but the effect of this modification on APP processing and formation of the Alzheimer’s disease associated amyloid-β (Aβ) peptide has so far not been investigated. Here, we demonstrate with pharmacological tools or siRNA that O-GlcNAcase and O-GlcNAc transferase regulate the level of O-GlcNAcylated APP. We also show that O-GlcNAcylation increases non-amyloidogenic α-secretase processing, resulting in increased levels of the neuroprotective sAPPα fragment and decreased Aβ secretion. Our results implicate O-GlcNAcylation as a potential therapeutic target for Alzheimer’s disease.

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AGROVOC Keywords

acetylglucosamine acylation acylation enzymology genetics humans metabolism oximes pharmacology phenylcarbamates rna secretion therapy

Bibliographic information

Published in

Biochemical and biophysical research communications

Volume 404 Issue 3 Pagination 882 - 886 ISSN 0006-291X

Publisher

Elsevier Inc.

Other Subjects

Small interfering rna; Drug effects; Cell line; Tumor; Antagonists & inhibitors; Alzheimer disease; Amyloid beta-protein precursor; Analogs & derivatives; Amyloid; Small interfering; Beta-n-acetylhexosaminidase; Gene knockdown techniques; Beta-n-acetylhexosaminidases; Alzheimer disease; N-acetylglucosaminyltransferases

Language

English

Type

Journal Article; Text

In AGRIS since: 2024-02-28

Format: MODS

Data Provider

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Links

DOI http://dx.doi.org/10.1016/j.bbrc.2010.12.080

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