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C Crone J Frokjaer-Jensen JJ Friedman O Christensen 《The Journal of general physiology》1978,71(2):195-220
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Most cellular processes descend into failure during aging. While a large collection of longevity pathways has been identified in the past decades, the mechanism for age-related decline of cellular homeostasis and organelle function remains largely unsolved. It is known that many organelles undergo structural and functional changes during normal aging, which significantly contributes to the decline of tissue function at old ages. Since recent studies have revealed an emerging role of organelles as regulatory hubs in maintaining cellular homeostasis, understanding of organelle aging will provide important insights into the cellular basis of organismal aging. Here we review current progress on the characterization of age-dependent structural and functional alterations in the more well-studied organelles, as well as the known mechanisms governing organelle aging in model organisms, with a special focus on the fruit fly Drosophila melanogaster. 相似文献
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Heterocyclic ketones as inhibitors of histone deacetylase 总被引:1,自引:0,他引:1
Vasudevan A Ji Z Frey RR Wada CK Steinman D Heyman HR Guo Y Curtin ML Guo J Li J Pease L Glaser KB Marcotte PA Bouska JJ Davidsen SK Michaelides MR 《Bioorganic & medicinal chemistry letters》2003,13(22):3909-3913
Several heterocyclic ketones were investigated as potential inhibitors of histone deacetylase. Nanomolar inhibitors such as 22 and 25 were obtained, the anti-proliferative activity of which were shown to be mediated by HDAC inhibition. 相似文献
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Tong Y Claiborne A Pyzytulinska M Tao ZF Stewart KD Kovar P Chen Z Credo RB Guan R Merta PJ Zhang H Bouska J Everitt EA Murry BP Hickman D Stratton TJ Wu J Rosenberg SH Sham HL Sowin TJ Lin NH 《Bioorganic & medicinal chemistry letters》2007,17(13):3618-3623
A study on substitutions at the four open positions on the phenyl ring of the 1,4-dihydroindeno[1,2-c]pyrazoles as potent CHK-1 inhibitors is described. Bis-substitution at both the 6- and 7-positions led to inhibitors with IC(50) values below 0.3nM. The compound with the best overall activities (36) was able to potentiate the anti-proliferative effect of doxorubicin in HeLa cells by at least 47-fold. Physicochemical, metabolic, and pharmacokinetic properties of selected inhibitors are also disclosed. 相似文献