Isolation of signal molecules on the secretion of amyloid precursor

淀粉样蛋白前体分泌信号分子的分离

• 批准号: 08458259
• 负责人: ISHIURA Shoichi
• 金额: $ 4.35万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08458259/
• 关键词: Alzheimer's disease; Amyloid; Protease; Signal molecules; Processing; Secretion; ソーティング

Alzheimer's disease amyloid precursor protein (APP) has attracted attention due to its involvement in the deposition of amyloid beta protein found in brain of both sporadic and genetic Alzheimer's disease patients. It is accepted that APP undergoes tow different types of processing catalyzed by three hypothesized proteases. One type mediated by alpha-secretase involves the non-amyloidogenic pathway, which precludes the generation of the beta protein. The N-terminal large fragment of APP is secreted into serum.The intracellular sorting of APP has attracted much interest, because some sorting signals in APP molecule are highly involved in the fate of newly-synthesized APP.We constracted two mutants, APPE19 and APPdeltaC10, which contains or deletes an endoplasmic reticulum (ER) retention signal. Addition of ER retention signal inhibied secretion of APP,while deletion of it promoted secretion. These results suggest that these sequences are important for the secretion and intracellular metabolism of APP.

阿尔茨海默病淀粉样前体蛋白(APP)参与了散发性和遗传性阿尔茨海默病患者大脑中淀粉样β蛋白的沉积，因此引起了人们的关注。人们普遍认为，APP经历了两种不同类型的加工，由三种假想的蛋白水解酶催化。其中一种类型由α-分泌酶介导，涉及非淀粉样蛋白生成途径，这排除了β蛋白的产生。APP的N端大片段被分泌到血清中，由于APP分子中的一些分选信号与新合成的APP的命运密切相关，APP的细胞内分选引起了人们的极大兴趣。内质网滞留信号的加入抑制APP的分泌，而缺失则促进APP的分泌。这些结果表明，这些序列对APP的分泌和细胞内代谢是重要的。

项目成果

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