O-GlcNAcylation increases non-amyloidogenic processing of the amyloid-beta precursor protein (APP)
2011 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 404, no 3, 882-886 p.Article in journal (Refereed) Published
The amyloid-beta precursor protein (APP) was shown to be O-GlcNAcylated 15 years ago, but the effect of this modification on APP processing and formation of the Alzheimer's disease associated amyloid-beta (A beta) 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 alpha-secretase processing, resulting in increased levels of the neuroprotective sAPP alpha fragment and decreased A beta secretion. Our results implicate O-GlcNAcylation as a potential therapeutic target for Alzheimer's disease.
Place, publisher, year, edition, pages
2011. Vol. 404, no 3, 882-886 p.
Alzheimer's disease, Amyloid-beta, APP processing, O-linked glycosylation, alpha-Secretase
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:su:diva-67334DOI: 10.1016/j.bbrc.2010.12.080ISI: 000286848100023OAI: oai:DiVA.org:su-67334DiVA: diva2:470316
authorCount :22011-12-282011-12-282015-01-30Bibliographically approved