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Tenuigenin treatment decreases secretion of the Alzheimer′s disease amyloid beta-protein in cultured cells
Jia, HX; Jiang, Y; Ruan, Y; Zhang, YB; Ma, X; Zhang, JZ; Beyreuther, K; Tu, PF; Zhang, D
关键词tenuiginin amyloid beta-protein (A beta) C-terminal 99 amino acids of APP (C99) beta-secretase
刊名NEUROSCIENCE LETTERS
2004-08-26
DOI10.1016/j.neulet.2004.05.093
367期:1页:123-128
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]PRECURSOR PROTEIN
英文摘要

Amyloid beta-protein (Abeta) is a pivotal pathological factor in Alzheimer′s disease (AD). Tenuigenin, extracted from the Chinese herb Polygala tenuifolia, seems to ameliorate the reduction in cholinergic function on rat models induced by Abeta. To examine this therapeutic effect, we tested whether Tenuigenin could inhibit secretion of Abeta in neuroblastoma cells stably transfected with two amyloid precursor protein (APP) constructs: the APP695 cDNA (SH-SY5Y APP695) and the C-terminal 99 amino acid residues of APP plus the signal peptide (SH-SY5Y SPA4CT). Tenuigenin inhibited the secretion of Abeta and the C-terminal 99 amino acids of APP (C99) in SH-SY5Y APP695 cells, but did not change the Abeta and C99 levels in SH-SY5Y SPA4CT cells. Fluorescence Resonance Energy Transfer (FRET) assays showed that Tenuigenin inhibited the proteolytic activities of BACE1 (beta-secretase) on its substrate in vitro. In addition, Tenuigenin did not demonstrate any cytotoxic effects. nor did it affect APP mRNA expression, holoAPP synthesis or sAPPalpha(x secretion. Our data suggest that Tenuigenin can inhibit the secretion of Abeta in SH-SY5Y APP 695 cells via BACE1 inhibition. Taken together, these results suggest that Tenuigenin may be worthy of future study as an anti-AD drug. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

语种英语
WOS记录号WOS:000223531800028
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被引频次:59[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/60033
专题北京大学精神卫生研究所
作者单位1.Peking Univ, Coll Pharm, Beijing 100083, Peoples R China
2.Capital Univ, Beijing Anding Hosp, Beijing 100088, Peoples R China
3.Peking Univ, Dept Biochem, Inst Mental Hlth, Beijing 100083, Peoples R China
4.Univ Heidelberg, Ctr Mol Biol, D-69120 Heidelberg, Germany
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GB/T 7714
Jia, HX,Jiang, Y,Ruan, Y,et al. Tenuigenin treatment decreases secretion of the Alzheimer′s disease amyloid beta-protein in cultured cells[J]. NEUROSCIENCE LETTERS,2004,367(1):123-128.
APA Jia, HX.,Jiang, Y.,Ruan, Y.,Zhang, YB.,Ma, X.,...&Zhang, D.(2004).Tenuigenin treatment decreases secretion of the Alzheimer′s disease amyloid beta-protein in cultured cells.NEUROSCIENCE LETTERS,367(1),123-128.
MLA Jia, HX,et al."Tenuigenin treatment decreases secretion of the Alzheimer′s disease amyloid beta-protein in cultured cells".NEUROSCIENCE LETTERS 367.1(2004):123-128.
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