PILOT PROJECT-- IDENTIFICATION OF BETA AMYLOID PROTEIN SECRETASE

试点项目——β淀粉样蛋白分泌酶的鉴定

• 批准号: 6267400
• 负责人: STEVEN YOUNKIN
• 金额: $ 13.91万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2000-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6267400
• 关键词: amyloid proteins; endopeptidases; flow cytometry; protein metabolism; protein purification; tissue /cell culture

With the recent demonstration by this laboratory and others (i) that the amyloid beta protein precursor (betaAPP) is constitutively processed by betaAPP secretase to produce identifiable derivatives, (ii) that the endosomal-lysosomal system processes identifiable carboxyl-terminal betaAPP derivatives likely to be important intermediates in the pathway that produces amyloid, and (iii) that 4 kD amyloid beta protein (Abeta) is normally produced and released by cultured cells, it is now realistic to undertake the identification of the key proteases that determine the amount of Abeta produced. Here, we propose experimentation focused on the identification of betaAPP secretase that will explore the feasibility of rapidly identifying these proteases using antisense cDNA expression libraries. We plan to focus on betaAPP secretase in these experiments because it is likely to be difficult to isolate this unusual and critically important enzyme conventionally using in vitro assays based on sequence specificity and because the knockout of betaAPP secretase with antisense cDNAs will almost certainly increase the level of surface betaAPP to a degree that can be detected by fluorescence activated cell sorting.

随着这个实验室和其他实验室最近的证明(1)