APP overexpression

Our research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 mice. Indeed, overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer's disease.

Analogue results were obtained for cells overexpressing an APP mutant that cannot be processed by α-secretase, highlighting the major influence of cholesterol enrichment on the cleavage of APP carried out by Bace1. By contrast, the cholesterol content was not correlated with changes in membrane dynamics of APP and Bace1 analyzed with single molecule tracking, indicating that the effect of cholesterol enrichment on APP processing by Bace1 is uncoupled from changes in their lateral diffusion.

Overexpression of CCN1 in ESCC cells induced cell cycle arrest rather than apoptosis through upregulation of APP and its association with p53 without DR6 involvement. Overexpression of APP stopped cell growth, but overexpression of DR6 did not cause any form of programmed cell death or cell cycle arrest whatsoever.

Overexpression of CCN1 in ESCC cells inhibited cell proliferation through upregulation of APP and its association with p53 without DR6 involvement. Overexpression of APP stopped cell growth, but overexpression of DR6 did not affect cell growth or cell death whatsoever.

Further, reduced cell proliferation was seen under hypoxic conditions compared to normoxic conditions indicating that hypoxic conditions further exacerbateAD pathology. Our findings in an in vitro AD model, suggest that sulindac has a potential therapeutic value to ameliorate AD pathology.

In the hippocampus of miR-455 null mice at 14 months of age, the levels of protein for APP, BACE1 and TAU were all increased. Such findings reinforce the involvement of miR-455 in AD progression and demonstrate its action on cognitive performance.

These results indicate that O-GlcNAcylation can regulate lipid raft-dependent APP endocytosis via translocation of APP into non-raft microdomains. Our findings showed a new functional role of O-GlcNAcylation for the regulation of APP trafficking, offering new mechanistic insight for Aβ production.