Protection of PMS777, a New AChE Inhibitor with PAF Antagonism, Against Amyloid-beta-Induced Neuronal Apoptosis and Neuroinflammation.
 

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02-06-09 08:15 AM
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Protection of PMS777, a New AChE Inhibitor with PAF Antagonism, Against Amyloid-beta-Induced Neuronal Apoptosis and Neuroinflammation.
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Protection of PMS777, a New AChE Inhibitor with PAF Antagonism, Against Amyloid-beta-Induced Neuronal Apoptosis and Neuroinflammation.

Cell Mol Neurobiol. 2009 Feb 5;

Authors: Li J, Hu J, Shao B, Zhou W, Cui Y, Dong C, Ezoulin JM, Zhu X, Ding W, Heymans F, Chen H

Amyloid-beta (Abeta) 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 Abeta-induced neuronal apoptosis in vitro and neuroinflammation in vivo. PMS777 (1-100 muM) was found to inhibit Abeta-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 Abeta. In vivo experimental study demonstrated that PMS777 could attenuate Abeta-induced microglial and astrocytic activation in the rat hippocampus after systemic administration. These results suggest that PMS777 potently protects against Abeta-induced neuronal apoptosis and neuroinflammation, and warrants further investigations in connection with its potential value in the treatment of Alzheimer's disease.

PMID: 19194797 [PubMed - as supplied by publisher]