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Updated: Jul 2, 2026

A11-positive β-amyloid Oligomer Preparation and Assessment Using Dot Blotting Analysis
Published on: May 22, 2018
PMS777, a new cholinesterase inhibitor with anti-platelet activated factor activity, regulates amyloid precursor
Hong-Qi Yang1, Zhi-Kun Sun, Yan-Xin Zhao
1Department of Neurology, Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
Abstract:
Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by progressive impairment of memory and cognition. Previous data have shown that beta-amyloid (Abeta) cascade plays a central role in AD pathophysiology and thus drugs regulate amyloid precursor protein (APP) metabolism may have therapeutic potential. Here the effects of PMS777, a new cholinesterase inhibitor with anti-platelet activated factor activity, on APP processing were investigated. Using SH-SY5Y(APP695) cells, it showed that PMS777 treatment caused significant decreased secretion of sAPPalpha into the conditioned media without affecting cellular holoAPP synthesis. When PC12 cells were incubated with PMS777, the same effect was observed. The data also indicated that 10 muM PMS777 incubation decreased the release of Abeta42 into the cell media as compared with vehicle group in SH-SY5Y(APP695) cells. Pretreatment of cells with M-receptor scopolamine antagonized the decreased secretion of sAPPalpha induced by PMS777, but N-receptor alpha-bungarotoxin pretreatment did not have such an effect. These results indicated that PMS777 could modulate APP processing in vitro and that decreasing Abeta generation might demonstrate its therapeutic potential in AD.
Insights
PMS777, a novel drug, reduces beta-amyloid (Abeta) production by modulating amyloid precursor protein (APP) processing. This suggests PMS777 may offer therapeutic potential for Alzheimer's disease (AD).
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Alzheimer's disease (AD) is a neurodegenerative disorder marked by memory and cognitive decline.
- The beta-amyloid (Abeta) cascade is a key factor in AD pathophysiology.
- Modulating amyloid precursor protein (APP) metabolism is a potential therapeutic strategy for AD.
Purpose of the Study:
- To investigate the effects of PMS777, a cholinesterase inhibitor with anti-platelet activated factor activity, on APP processing.
- To determine if PMS777 influences the generation of Abeta, a critical component in AD.
Main Methods:
- Experiments were conducted using SH-SY5Y(APP695) and PC12 cell lines.
- Cells were treated with PMS777, and the secretion of sAPPalpha and Abeta42 was measured.
- Receptor antagonists (scopolamine and alpha-bungarotoxin) were used to explore the mechanism of action.
Main Results:
- PMS777 significantly decreased the secretion of sAPPalpha in both cell lines without affecting holoAPP synthesis.
- PMS777 treatment reduced the release of Abeta42 in SH-SY5Y(APP695) cells.
- Scopolamine pretreatment antagonized the effect of PMS777 on sAPPalpha secretion, while alpha-bungarotoxin did not.
Conclusions:
- PMS777 demonstrates the ability to modulate APP processing in vitro.
- The drug's capacity to decrease Abeta generation indicates its potential therapeutic value for Alzheimer's disease.
- The mechanism appears to involve M-receptor pathways.
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