Abstract
Amyloid-β (Aβ) plays a central role in the neuroinflammation and cholinergic neuronal apoptosis in Alzheimer’s disease, and thus has been considered as a main determinant of this disease. In the previous study, we reported that PMS777, a novel bis-interacting ligand for acetylcholinesterase (AChE) inhibition and platelet-activating factor (PAF) receptor antagonism, could significantly attenuate PAF-induced neurotoxicity. Continuing our efforts, we further investigated the protective effect of PMS777 on Aβ-induced neuronal apoptosis in vitro and neuroinflammation in vivo. PMS777 (1–100 μM) was found to inhibit Aβ-induced human neuroblastoma SH-SY5Y cell apoptosis in a concentration-dependent manner. Concurrently, PMS777 increased ratio of bcl-2 to bax mRNA, and inhibited both mRNA expression and activity of caspase-3 in SH-SY5Y cells after the exposure with Aβ. In vivo experimental study demonstrated that PMS777 could attenuate Aβ-induced microglial and astrocytic activation in the rat hippocampus after systemic administration. These results suggest that PMS777 potently protects against Aβ-induced neuronal apoptosis and neuroinflammation, and warrants further investigations in connection with its potential value in the treatment of Alzheimer’s disease.
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Acknowledgments
We gratefully thank the National Natural Science Foundation of China (No. 30772553), the Major Basic Research Project of Shanghai Municipal Science and Technology Commission (07DJ14005) and the Research Project for young teachers from Institute of Medical Sciences for financial support.
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The authors Juan Li and Jinjia Hu contributed equally to this article.
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Li, J., Hu, J., Shao, B. et al. Protection of PMS777, a New AChE Inhibitor with PAF Antagonism, Against Amyloid-β-Induced Neuronal Apoptosis and Neuroinflammation. Cell Mol Neurobiol 29, 589–595 (2009). https://doi.org/10.1007/s10571-009-9351-0
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DOI: https://doi.org/10.1007/s10571-009-9351-0