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KMID : 0370220070510040264
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Yakhak Hoeji
2007 Volume.51 No. 4 p.264 ~ p.269
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Effects of Radicicol on the Metabolism of ${\beta}-Amyloid$ Precursor Protein in Neuroblastoma Cells
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Leem Jae-Yoon
Lee Ri-Hua
Lee Kyung-A
Gong Du-Gyun
Choi Bu-Jin
Lee Choong-Soo
Eun Jae-Soon
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Abstract
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Alzheimer’s disease (AD) is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}-amyloid $ (A ${\beta}$) peptides, which are generated by processing of amyloid precursor protein (APP). It is urgent to develop effective therapies for the treatment of AD, since our society rapidly accelerate aging. A${\beta}$ peptides have been believed to be neurotoxic and now are also considered to have effects on the mechanism of memory formation. In this study, effects of radicicol on the metabolism of APP were analyzed. Radicicol inhibited the secretion of A${\beta}$ from the Neuro2a cell line (APPswe cell) expressing APPswe. Beta-site APP cleaving enzyme (BACE) fluorescence resonance energy transfer (FRET) assay revealed that it inhibited BACE activity in a dose dependently manner. Immunoblotting study showed that it inhibited intracellular heat shock protein (HSP)90 and it increased the secretion of HSP90 from the APPswe cells. We suggest that radicicol inhibits APP metabolism and Ap generation by the means of HSP90 inhibitory mechanism and partially BACE inhibitory mechanism. This is the first report that radicicol inhibits the secretion of A${\beta}$ peptides from neuroblastoma cells.
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KEYWORD
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Alzheimer’s disease, ${\beta}-amyloid$ peptides, radicicol, APPswe, BACE, HSP90
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