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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2009-6-11
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pubmed:abstractText |
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 microM) 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.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1573-6830
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pubmed:author |
pubmed-author:ChenHongzhuanH,
pubmed-author:CuiYongyaoY,
pubmed-author:DingWenlongW,
pubmed-author:DongChangzhiC,
pubmed-author:EzoulinJean-Marc MiezanJM,
pubmed-author:HeymansFrançoiseF,
pubmed-author:HuJinjiaJ,
pubmed-author:LiJuanJ,
pubmed-author:ShaoBiyunB,
pubmed-author:ZhouWeiW,
pubmed-author:ZhuXuX
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pubmed:issnType |
Electronic
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
589-95
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:19194797-Amyloid beta-Peptides,
pubmed-meshheading:19194797-Animals,
pubmed-meshheading:19194797-Apoptosis,
pubmed-meshheading:19194797-Caspase 3,
pubmed-meshheading:19194797-Cell Line, Tumor,
pubmed-meshheading:19194797-Cell Survival,
pubmed-meshheading:19194797-Cholinesterase Inhibitors,
pubmed-meshheading:19194797-Furans,
pubmed-meshheading:19194797-Humans,
pubmed-meshheading:19194797-Inflammation,
pubmed-meshheading:19194797-Neurons,
pubmed-meshheading:19194797-Platelet Activating Factor,
pubmed-meshheading:19194797-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:19194797-Rats,
pubmed-meshheading:19194797-Rats, Sprague-Dawley,
pubmed-meshheading:19194797-bcl-2-Associated X Protein
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pubmed:year |
2009
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pubmed:articleTitle |
Protection of PMS777, a new AChE inhibitor with PAF antagonism, against amyloid-beta-induced neuronal apoptosis and neuroinflammation.
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pubmed:affiliation |
Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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