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• W2010592788 abstract "Chalcone compounds have been widely studied for their anti-inflammatory, anti-pyretic, anti-invasive and anti-proliferative activities in various cell lines. However, their effects on the central nervous system (CNS) are still largely unexplored. We have recently developed a bioconversion system using a recombinant Escherichia coli that enables us to produce chemical compounds that are naturally rare and usually difficult to chemically synthesize. One such compound is 3-(2,3-dihydroxyphenyl)-1-phenylpropan-1-one, a novel chalcone-diol. Here we show, for the first time, that the chalcone-diol enhanced the phosphorylation of extracellular signal-regulated kinase (ERK) in a time- and concentration-dependent manner in cultured cortical neurons. Also, this chalcone-diol increased intracellular cyclic AMP (cAMP) concentration, thereby enhancing phosphorylation of ERK and cAMP-response element-binding protein (CREB), and CRE-mediated transcription via the cAMP-dependent protein kinase (PKA)/mitogen-activated protein kinase/ERK kinase (MEK) pathway in cultured rat hippocampal neurons. Recent studies have demonstrated that PKA/CREB-dependent signaling, which is required for long-term potentiation, is inhibited by sublethal concentrations of amyloid beta-peptide (Abeta) in cultured hippocampal neurons. After treatment with the chalcone-diol at 50 muM prior to treatment with a sublethal concentration of Abeta(1-42), the Abeta(1-42)-induced inhibition of phosphorylation of PKA substrates and CREB was prevented in cultured hippocampal neurons, indicating the potential for protection against the Abeta-induced impairment of PKA/CREB signaling observed in Alzheimer's disease. Therefore, these results suggest that our present study provides a new approach for discovering novel lead compounds for the treatment of neurodegenerative CNS diseases associated with impaired PKA/CREB signaling, including Alzheimer's disease." @default.
• W2010592788 created "2016-06-24" @default.
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• W2010592788 date "2008-12-01" @default.
• W2010592788 modified "2023-10-18" @default.
• W2010592788 title "A novel diol-derivative of chalcone produced by bioconversion, 3-(2,3-dihydroxyphenyl)-1-phenylpropan-1-one, activates PKA/MEK/ERK signaling and antagonizes Aβ-inhibition of the cascade in cultured rat CNS neurons" @default.
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• W2010592788 doi "https://doi.org/10.1016/j.ejphar.2008.09.046" @default.
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