Tenuigenin treatment decreases secretion of the Alzheimer's disease amyloid β-protein in cultured cells
Tenuigenin treatment decreases secretion of the Alzheimer's disease amyloid β-protein in cultured cells
复制标题
DOI：
10.1016/j.neulet.2004.05.093
复制
发表时间：
2004-08-26
影响因子：
2.5
通讯作者：
Zhang, D
中科院分区：
文献类型：
--
作者：
Jia, HX;Jiang, Y;Zhang, D
淀粉样β蛋白（Amyloidbeta-protein，Abeta）是阿尔茨海默病（Alzheimer 'sdisease，AD）的重要病理因子。从中药远志中提取的远志皂苷元似乎可以改善Abeta诱导的大鼠模型的胆碱能功能降低。为了检查这种治疗效果，我们测试了Tenuigenin是否可以抑制用两种淀粉样前体蛋白（APP）构建体稳定转染的神经母细胞瘤细胞中的Abeta分泌：APP 695 cDNA（SH-SY 5 Y APP 695）和APP的C-末端99个氨基酸残基加上信号肽（SH-SY 5 Y SPA 4 CT）。Tenuigenin抑制SH-SY 5 Y APP 695细胞分泌A β和APP C端99个氨基酸（C99），但不影响SH-SY 5 Y SPA 4CT细胞分泌A β和C99。荧光共振能量转移（FRET）实验表明，Tenuigenin在体外可抑制BACE 1（β-分泌酶）对其底物的蛋白水解活性。此外，Tenuigenin未显示任何细胞毒性作用。也不影响APP mRNA表达、holoAPP合成或sAPP α β分泌。我们的数据表明，Tenuigenin可以通过抑制BACE 1来抑制SH-SY 5 Y APP 695细胞中Abeta的分泌。综上所述，这些结果表明，Tenuigenin可能是值得未来研究的抗AD药物。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
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.