Alzheimer’s disease is the most common form of dementia in the eldery. The peoples with Alzheimer’s disease have lost memory and declined cognition. Recently, the number of Alzheimer’s disease was estimated to be 6 million worldwide. The increasing number of people with Alzheimer’s disease is a grea...
Alzheimer’s disease is the most common form of dementia in the eldery. The peoples with Alzheimer’s disease have lost memory and declined cognition. Recently, the number of Alzheimer’s disease was estimated to be 6 million worldwide. The increasing number of people with Alzheimer’s disease is a great challenge for society. However, there is no cure. Epidemiological studies have documented a reduced prevalence of Alzheimer’s disease among users of nonsteroidal anti-inflammatory drugs (NSAIDs). It has been proposed that NSAIDs exert their beneficial effects in part by reducing neurotoxic inflammatory responses in the brain. The NSAIDs ibuprofen, indomethacin, and sulindac sulphide decrease, by as much as 80%, the amount of Aβ42 secreted from a variety of cultured cells. In contrast, other NSAIDs (e.g., sulindac sulphone, naproxen) did not reduce Aβ42 level. Because naproxen is a COX inhibitor, the results suggested that COX inhibition is not essential to the reduction of Aβ42. however, the mechanism of action of NSAIDs is not still known. In this study, our purpose is find out candidates that influence to the mechanism anti-amyloidogenic by NSAIDs. Therefore we used COX-1.2 double KO mouse neuronal EF-2X ML cell line. We used commonly 2 NSAIDs ibuprofen, naproxen, because ibuprofen and naproxen are structurally related. However, only ibuprofen reduces Aβ and not naproxen. As we used the structurally similar drug, we want to remove the proteins that may not be influenced pathogenesis of AD. Therefore, two-dimensional gel electrophoresis combined with mass spectrometry was used to analyze change in the proteome of DMSO (control)-treated compared with ibuprofen and naproxen treated EF-2X ML cell line. Six gels obtained for each sample were analyzed by image analysis software, PDQuest. Using PDQuest, the intensities of protein spots obtained from each gel were compared using statistical analysis. There were 36 and 35 protein spots showing the change of expression level when ibuprofen and naproxen were treated, respectively with the statistical significance (p < 0.05). Then we was selected only changed proteins by ibuprofen treated cell. The proteins in the cells that were differentially expressed following treatment with ibuprofen were identified by peptide mass fingerprinting. Total 20 protein spots were identified. They include vimentin, 78KDa glucose-regulated protein precursor, transitional endoplasmic reticulum ATPase, stress-induced phosphoprotein 1 etc. We have assumed that these proteins may be candidates related the mechanism reducing Aβ42 by NSAIDs. To confirm the expression level, several proteins were examined using western blot analysis. As we found candidates involved mechanism of anti-amyloidogenic by NSAIDs, it will be helpful not only to reveal the mechanism reducing Aβ by NSAIDs but also to develop new therapy.
Alzheimer’s disease is the most common form of dementia in the eldery. The peoples with Alzheimer’s disease have lost memory and declined cognition. Recently, the number of Alzheimer’s disease was estimated to be 6 million worldwide. The increasing number of people with Alzheimer’s disease is a great challenge for society. However, there is no cure. Epidemiological studies have documented a reduced prevalence of Alzheimer’s disease among users of nonsteroidal anti-inflammatory drugs (NSAIDs). It has been proposed that NSAIDs exert their beneficial effects in part by reducing neurotoxic inflammatory responses in the brain. The NSAIDs ibuprofen, indomethacin, and sulindac sulphide decrease, by as much as 80%, the amount of Aβ42 secreted from a variety of cultured cells. In contrast, other NSAIDs (e.g., sulindac sulphone, naproxen) did not reduce Aβ42 level. Because naproxen is a COX inhibitor, the results suggested that COX inhibition is not essential to the reduction of Aβ42. however, the mechanism of action of NSAIDs is not still known. In this study, our purpose is find out candidates that influence to the mechanism anti-amyloidogenic by NSAIDs. Therefore we used COX-1.2 double KO mouse neuronal EF-2X ML cell line. We used commonly 2 NSAIDs ibuprofen, naproxen, because ibuprofen and naproxen are structurally related. However, only ibuprofen reduces Aβ and not naproxen. As we used the structurally similar drug, we want to remove the proteins that may not be influenced pathogenesis of AD. Therefore, two-dimensional gel electrophoresis combined with mass spectrometry was used to analyze change in the proteome of DMSO (control)-treated compared with ibuprofen and naproxen treated EF-2X ML cell line. Six gels obtained for each sample were analyzed by image analysis software, PDQuest. Using PDQuest, the intensities of protein spots obtained from each gel were compared using statistical analysis. There were 36 and 35 protein spots showing the change of expression level when ibuprofen and naproxen were treated, respectively with the statistical significance (p < 0.05). Then we was selected only changed proteins by ibuprofen treated cell. The proteins in the cells that were differentially expressed following treatment with ibuprofen were identified by peptide mass fingerprinting. Total 20 protein spots were identified. They include vimentin, 78KDa glucose-regulated protein precursor, transitional endoplasmic reticulum ATPase, stress-induced phosphoprotein 1 etc. We have assumed that these proteins may be candidates related the mechanism reducing Aβ42 by NSAIDs. To confirm the expression level, several proteins were examined using western blot analysis. As we found candidates involved mechanism of anti-amyloidogenic by NSAIDs, it will be helpful not only to reveal the mechanism reducing Aβ by NSAIDs but also to develop new therapy.
Keyword
#마우스 신경세포 Ibuprofen Naproxen처리
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