Human wild presenilin-1 mimics the effect of the mutant presenilin-1 on the processing of Alzheimer's amyloid precursor protein in PC12D cells
Human wild presenilin-1 mimics the effect of the mutant presenilin-1 on the processing of Alzheimer's amyloid precursor protein in PC12D cells
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DOI：
10.1016/s0022-510x(01)00543-3
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发表时间：
2001-07-15
影响因子：
4.4
通讯作者：
Mori, H
中科院分区：
文献类型：
--
作者：
Kametani, F;Tanaka, K;Mori, H
大多数家族性早发性阿尔茨海默病（FAD）是由早老素-I（PSI）基因突变引起的。β 42衍生自淀粉样前体蛋白（APP），并且浓度增加被广泛认为是PS功能异常的病理标志。因此，PS 1和APP之间的相互作用是AD的分子机制的核心。研究野生型人PS1对大鼠APP代谢的影响。我们建立了几种表达人野生型或突变型PS1的PC 12 D细胞系，并分析了内源性大鼠APP的加工和细胞内γ-分泌酶活性。我们发现在表达野生型人PS1的PC 12 D细胞中A β 42/A β 40的比率增加。这些变化与在表达携带A260 V突变的人PS1的PC 12 D细胞中发现的变化相同。这些结果表明，APP代谢是生理调节的PS1和正常PS1的损失影响γ-分泌酶活性。(C)2001 Elsevier Science B. V.保留所有权利。
Most familial early-onset Alzheimer's disease (FAD) is caused by mutations in the presenilin-I (PSI) gene. A beta 42 is derived from amyloid precursor protein (APP) and increased concentrations are widely believed to be a pathological hallmark of abnormal PS function. Thus, the interaction between PS1 and APP is central to the molecular mechanism of AD. To examine the effect of wild-type human PS1 on rat APP metabolism. we made several PC12D cell lines that expressed human wild or mutant PS1, and analyzed the processing of endogenous rat APP and the intracellular gamma -secretase activity. We found the ratio of A beta 42/A beta 40 increased in PC12D cells expressing wild-type human PS1. These changes were identical to those found in PC12D cells expressing human PS1 bearing the A260V mutation. These results suggest that APP metabolism is physiologically regulated by the PS1 and that loss of normal PS1 affects gamma -secretase activity. (C) 2001 Elsevier Science B.V. All rights reserved.