l655240actingasacompetitivebace1inhibitorefficientlydecreasespamyloidpeptideproductioninhek293appswecells

	l655240actingasacompetitivebace1inhibitorefficientlydecreasespamyloidpeptideproductioninhek293appswecells
	Lu Qin 1; Chen Wuyan 2; Zhu Zhiyuan 2; Chen Jing 2; Xu Yechun 2; Kaewpet Morakot 3; Rukachaisirikul Vatcharin 3; Chen Lili 2; Shen Xu 1
刊名	actapharmacologicasinica
	2012
卷号	33 期号:12 页码:1459
关键词	L655 240 Alzheimer's disease BACE1 -amyloid peptide HEK293-APPswe cells
ISSN号	1671-4083
英文摘要	To identify a small molecule L655,240 as a novel -secretase (BACE1) inhibitor and to investigate its effects on -amyloid (A) generation in vitro. Methods: Fluorescence resonance energy transfer (FRET) was used to characterize the inhibitory effect of L655,240 on BACE1. Sur-face plasmon resonance (SPR) technology-based assay was performed to study the binding affinity of L655,240 for BACE1. The selectivity of L655,240 toward BACE1 over other aspartic proteases was determined with enzymatic assay. The effects of L655,240 on A40, A42, and sAPP production were studied in HEK293 cells stably expressing APP695 Swedish mutantK595N/M596L (HEK293-APPswe cells). The activities of BACE1, y-secretase and a-secretase were assayed, and both the mRNA and protein levels of APP and BACE1 were evaluated using real-time PCR (RT-PCR) and Western blot analysis. Results: L655,240 was determined to be a competitive, selective BACE1 inhibitor (IC50=4.471.37 mol/L), which bound to BACE1 directly (KD=17.90.72 mol/L). L655,240 effectively reduced A40, A42, and sAPP production by inhibiting BACE1 without affecting the activities of y-secretase and a-secretase in HEK293-APPswe cells. L655,240 has no effect on APP and BACE1 mRNA or protein levels in HEK293-APPswe cells. Conclusion: The small molecule L655,240 is a novel BACE1 inhibitor that can effectively decreases A production in vitro, thereby highlighting its therapeutic potential for the treatment of Alzheimer's disease.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/283742]
专题	中国科学院上海药物研究所
作者单位	1.华东理工大学 2.中国科学院上海药物研究所 3.宋卡王子大学
推荐引用方式 GB/T 7714	Lu Qin,Chen Wuyan,Zhu Zhiyuan,et al. l655240actingasacompetitivebace1inhibitorefficientlydecreasespamyloidpeptideproductioninhek293appswecells[J]. actapharmacologicasinica,2012,33(12):1459.
APA	Lu Qin.,Chen Wuyan.,Zhu Zhiyuan.,Chen Jing.,Xu Yechun.,...&Shen Xu.(2012).l655240actingasacompetitivebace1inhibitorefficientlydecreasespamyloidpeptideproductioninhek293appswecells.actapharmacologicasinica,33(12),1459.
MLA	Lu Qin,et al."l655240actingasacompetitivebace1inhibitorefficientlydecreasespamyloidpeptideproductioninhek293appswecells".actapharmacologicasinica 33.12(2012):1459.