Azure B affects amyloid precursor protein metabolism in PS70 cells


BİBEROĞLU K. , YÜKSEL M. , TACAL Ö.

CHEMICO-BIOLOGICAL INTERACTIONS, cilt.299, ss.88-93, 2019 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 299
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.cbi.2018.11.023
  • Dergi Adı: CHEMICO-BIOLOGICAL INTERACTIONS
  • Sayfa Sayıları: ss.88-93

Özet

Alzheimer's disease (AD), the most common form of dementia, is characterized by abundant deposition of amyloid-beta (A beta) peptide that is the result of sequential cleavage of amyloid precursor protein (APP) by beta-secretase and gamma-secretase. Several studies have documented that inhibition of A beta peptide synthesis or facilitating its degradation is one of the attractive therapeutic strategies in AD. Methylene blue (MethB), which has recently been investigated in Phase II clinical trials, is a prominent inhibitor in reducing A beta oligomers. Herein, we wonder whether the mitigating effects of MethB on amyloid metabolism are related to the activity of its major metabolite, azure B. The goal of this study was to investigate the effects of azure B, which is also a cholinesterase inhibitor, on APP processing by using Chinese hamster ovary cells stably expressing human wild-type APP and presenilin 1 (PS70). Azure B significantly decreased the levels of secreted APP alpha (sAPP alpha) and A beta(40/42) in culture medium with a dose-dependent manner. A significant decrease was also observed in the levels of intracellular APP without affecting the cell viability. In parallel with the decrease of APP and APP metabolites, the activity of beta-secretase 1 (BACE1) was significantly attenuated compared to control. Overall, our results show that azure B has a large contribution for the pharmacological profile of MethB in APP metabolism.