表没食子儿茶素没食子酸酯通过抑制BACE1转录和翻译减少Aβ生成  

EGCG Attenuates Amyloid-β Generation via Inhibiting the Transcription and Translation of BACE1

作　　者：闫玉芳[1] 龚锴[1] 马拓[1] 张秀芳[1] 公衍道[1] 

机构地区：[1]清华大学生命科学学院,生物膜与膜生物工程国家重点实验室,北京100084

出　　处：《生物物理学报》2013年第7期486-495,共10页Acta Biophysica Sinica

基　　金：生物膜与膜生物工程国家重点实验室基金项目;国家自然科学基金项目(30973068);清华裕元医学科学研究基金项目(20240000514)~~

摘　　要：研究表明绿茶多酚的主要成分表没食子儿茶素没食子酸酯(epigallocatechin-3-gallate,EGCG)可以改善阿尔茨海默症模型动物的认知功能障碍,但其作用机制尚不清楚。为探讨EGCG对淀粉样肽(amyloid-βpeptide,Aβ)代谢的影响及作用机制,用EGCG孵育N2a/Swe细胞24 h后,利用Western blot和ELISA方法检测淀粉样前体蛋白(amyloid precurson protein,APP)及其切割产物的水平。结果显示,EGCG能够显著降低Aβ的分泌水平,而对APP的蛋白表达水平没有明显影响。此外,EGCG显著降低了β分泌酶BACE1的mRNA水平、蛋白表达水平及BACE1剪切产物sAPPβ的水平。以上结果表明,EGCG能抑制BACE1的转录和翻译,降低其对APP的酶切活性,最终减少Aβ的生成,揭示了EGCG调控Aβ代谢的一个新的作用机制。It has been reported that epigallocatechin-3-gallate （EGCG） could improve cognitive functions in animal models of Alzheimer＇s disease, but the underlying mechanisms are not completely understood. In order to investigate the effects of EGCG on amyloid-β （Aβ） metabolism and its mechanisms, APP and its proteolytic products were determined by Western blotting and ELISA methods after incubation of N2a/Swe cells with EGCG for 24 h. The results showed that EGCG treatment significantly decreased the levels of AI^40 and AI342 secreted in N2a/Swe cells. Additionally, there was no significant change in APP level after EGCG treatment. Treatment of EGCG dramatically reduced the mRNA and protein expression levels of BACEI. Moreover, EGCG treatment resulted in a reduction of protein level of sAPPβ, an APP fragment cleavaged by BACEI. These results suggest that EGCG inhibits the transcription and translation of BACE1, suppresses the activity of BACE1, and ultimately attenuates Aβ generation, which provides a novel mechanism for the regulation of Aβ metabolism by EGCG.

关 键 词：阿尔茨海默症 淀粉样肽 表没食子儿茶素没食子酸酯 Β分泌酶 

分 类 号：Q189[生物学—神经生物学]