کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1930794 | 1050527 | 2011 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: O-GlcNAcylation increases non-amyloidogenic processing of the amyloid-β precursor protein (APP) O-GlcNAcylation increases non-amyloidogenic processing of the amyloid-β precursor protein (APP)](/preview/png/1930794.png)
The amyloid-β 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-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.
Research highlights
► O-GlcNAcylation of amyloid-beta precursor protein (APP) is increased by PUGNAc.
► PUGNAc increases non-amyloidogenic processing of APP.
► PUGNAc decreases formation of amyloid-beta.
Journal: Biochemical and Biophysical Research Communications - Volume 404, Issue 3, 21 January 2011, Pages 882–886