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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2001-10-5
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pubmed:abstractText |
1. The accumulation of amyloid beta protein (Abeta) in the brain is a characteristic feature of Alzheimer's disease (AD). Clinical trials of AD patients with nonsteroidal anti-inflammatory drugs (NSAIDs) indicate a clinical benefit. NSAIDs are presumed to act by suppressing inhibiting chronic inflammation in the brain of AD patients. 2. In the present study, we investigated effects of S-2474 on Abeta-induced cell death in primary cultures of rat cortical neurons. 3. S-2474 is a novel NSAID, which inhibits cyclo-oxygenase-2 (COX-2) and contains the di-tert-butylphenol antioxidant moiety. S-2474 significantly prevented neurons from Abeta(25 - 35)- and Abeta(1 - 40)-induced cell death. S-2474 ameliorated Abeta-induced apoptotic features such as the condensation of chromatin and the fragmentation of DNA completely. 4. Prior to cell death, Abeta(25 - 35) generated prostaglandin D(2) (PGD(2)) and free radicals from neurons. PGD(2) is a product of cyclo-oxygenase (COX), and caused neuronal cell death. 5. S-2474 significantly inhibited the Abeta(25 - 35)-induced generation of PGD(2) and free radicals. 6. The present cortical cultures contained little non-neuronal cells, indicating that S-2474 affected neuronal survival directly, but not indirectly via non-neuronal cells. Both an inhibitory effect of COX-2 and an antioxidant effect might contribute to the neuroprotective effects of S-2474. 7. In conclusion, S-2474 exhibits protective effects against neurotoxicity of Abeta. Furthermore, the present study suggests that S-2474 may possess therapeutic potential for AD via ameliorating degeneration in neurons as well as suppressing chronic inflammation in non-neuronal cells.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/11588123-10095023,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11588123-10366679,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11588123-10821716,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11588123-10995830,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11588123-11079552,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11588123-11277593,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11588123-1346802,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11588123-1400587,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11588123-1497677,
http://linkedlifedata.com/resource/pubmed/commentcorrection/11588123-1673054,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/11588123-2218531,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/11588123-6195926,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/11588123-6438380,
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http://linkedlifedata.com/resource/pubmed/commentcorrection/11588123-9920782
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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 |
Oct
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pubmed:issn |
0007-1188
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
134
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
673-81
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11588123-Amyloid beta-Peptides,
pubmed-meshheading:11588123-Animals,
pubmed-meshheading:11588123-Anti-Inflammatory Agents, Non-Steroidal,
pubmed-meshheading:11588123-Cell Death,
pubmed-meshheading:11588123-Cells, Cultured,
pubmed-meshheading:11588123-Cerebral Cortex,
pubmed-meshheading:11588123-Cyclic S-Oxides,
pubmed-meshheading:11588123-Dose-Response Relationship, Drug,
pubmed-meshheading:11588123-Embryo, Mammalian,
pubmed-meshheading:11588123-Female,
pubmed-meshheading:11588123-Neurons,
pubmed-meshheading:11588123-Pregnancy,
pubmed-meshheading:11588123-Rats,
pubmed-meshheading:11588123-Rats, Sprague-Dawley,
pubmed-meshheading:11588123-Thiazoles
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pubmed:year |
2001
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pubmed:articleTitle |
Effects of S-2474, a novel nonsteroidal anti-inflammatory drug, on amyloid beta protein-induced neuronal cell death.
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pubmed:affiliation |
Discovery Research Laboratories, Shionogi and Co. Ltd., 12-4 Sagisu 5-Chome, Fukushima-ku, Osaka 553-0002, Japan. tatsurou.yagami@shionogi.co.jp
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pubmed:publicationType |
Journal Article
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