Effects of non-steroidal anti-inflammatory drugs on Abeta deposition in Abeta(1-42) transgenic C. elegans.
Although epidemiological studies have shown that long-term treatment with non-steroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer's disease (AD), the mechanism(s) by which NSAIDs reduce the risk of AD remain to be determined. As C. elegans possess neither inflammatory cells nor the arachidonate cascade, we could evaluate the effects of NSAIDs on amyloid beta (Abeta) deposition in the absence of immune cells using Abeta-transgenic C. elegans. For this purpose, we established a strain of Abeta-transgenic C. elegans in which thioflavin S-reactive deposits are reproducibly detectable by confocal microscopy. Among the NSAIDs examined, ibuprofen and naproxen reduced the number of thioflavin S-reactive deposits. Furthermore, ibuprofen and naproxen neither affect the thioflavin S binding to Abeta nor Abeta expression in transgenic C. elegans. These data suggest that ibuprofen and naproxen, the most frequently used NSAIDs for the treatment of AD, have an inhibitory effect on Abeta deposition that is independent of the arachidonate cascade and cellular immune systems.
Morita
Masahiko
M
Department of Neuroscience, Pharmacology Research Labs, Astellas Pharma Inc., Miyukigaoka Research Center, 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. masahiko.morita@jp.astellas.com
Osoda
Kazuhiko
K
Yamazaki
Mayako
M
Shirai
Fumiyuki
F
Matsuoka
Nobuya
N
Arakawa
Hiroyuki
H
Nishimura
Shintaro
S
D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D052160:Benzothiazoles; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism; D004008:Diclofenac / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D018613:Microscopy, Confocal; D013844:Thiazoles
D016229:Amyloid beta-Peptides; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052160:Benzothiazoles; D013844:Thiazoles; D004008:Diclofenac; C009462:thioflavin T; D007052:Ibuprofen; D007213:Indomethacin