Title : Effects of phenothiazine-structured compounds on APP processing in Alzheimer's disease cellular model - Yuksel_2017_Biochimie_138_82 |
Author(s) : Yuksel M , Biberoglu K , Onder S , Akbulut KG , Tacal O |
Ref : Biochimie , 138 :82 , 2017 |
Abstract :
The excess accumulation of amyloid-beta (Abeta) peptides derived from the sequential cleavage of amyloid precursor protein (APP) by secretases, is one of the toxic key events leading to neuronal loss in Alzheimer's disease (AD). Studies have shown that cholinergic activity may also be involved in the regulation of APP metabolism. In the current study, we have investigated the roles of toluidine blue O (TBO) and thionine (TH), newly recognized phenothiazine-derived cholinesterase inhibitors, on the metabolism of APP in Chinese hamster ovary cells stably expressing human APP751 and presenilin 1 (PS70 cells). We assessed the effects of both compounds on the levels of Abeta, soluble APP-alpha (sAPPalpha), intracellular APP and beta-site APP-cleaving enzyme 1 (BACE1). After treatment of PS70 cells with TBO or TH without any side effect on cell viability, the levels of secreted Abeta40, Abeta42 and sAPPalpha were assayed by specific sandwich ELISAs while APP and BACE1 in cell lysates were analyzed using Western blot. The secreted Abeta40, Abeta42 and sAPPalpha in TBO- and TH-treated cells were found to be reduced in a dose-dependent manner compared to vehicle-treated cells. Results suggest that TH mitigated the Abeta pathology by lowering APP levels whereas reduced Abeta caused by TBO treatment seems to be the outcome of both less substrate availability and amyloidogenic APP processing. Taken together, our results represent the first report demonstrating that TBO and TH can affect amyloid metabolism in vitro. |
PubMedSearch : Yuksel_2017_Biochimie_138_82 |
PubMedID: 28457944 |
Yuksel M, Biberoglu K, Onder S, Akbulut KG, Tacal O (2017)
Effects of phenothiazine-structured compounds on APP processing in Alzheimer's disease cellular model
Biochimie
138 :82
Yuksel M, Biberoglu K, Onder S, Akbulut KG, Tacal O (2017)
Biochimie
138 :82