RELEASE OF EXCESS AMYLOID BETA-PROTEIN FROM A MUTANT AMYLOID BETA-PROTEIN PRECURSOR
RELEASE OF EXCESS AMYLOID BETA-PROTEIN FROM A MUTANT AMYLOID BETA-PROTEIN PRECURSOR
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DOI：
10.1126/science.8424174
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发表时间：
1993-01-22
期刊：
影响因子：
56.9
通讯作者：
YOUNKIN, SG
中科院分区：
文献类型：
--
作者：
CAI, XD;GOLDE, TE;YOUNKIN, SG
在阿尔茨海默病（AD）中形成纤维沉积的4千道尔顿β淀粉样蛋白（Abeta）来源于一种被称为β淀粉样蛋白前体（betaAPP）的大蛋白。用表达野生型betaAPP或突变型betaAPP（DELTANL）的构建体转染人神经母细胞瘤（M17）细胞，比较了最近与家族性AD相关的betaAPP。连续代谢标记8小时后，表达betaAPP（DELTANL）的细胞比表达野生型betaAPP的细胞含有5倍多的含betaAPP的羧基端betaAPP衍生物，并向培养基中释放6倍多的Abeta。因此，这种突变的β - app可能会导致AD，因为它的处理方式发生了改变，释放了更多的β。
The 4-kilodalton amyloid beta protein (Abeta), which forms fibrillar deposits in Alzheimer's disease (AD), is derived from a large protein referred to as the amyloid beta protein precursor (betaAPP). Human neuroblastoma (M17) cells transfected with constructs expressing wild-type betaAPP or a mutant, betaAPP(DELTANL), recently linked to familial AD were compared. After continuous metabolic labeling for 8 hours, cells expressing betaAPP(DELTANL) had five times more of an Abeta-bearing, carboxyl terminal, betaAPP derivative than cells expressing wild-type betaAPP and they released six times more Abeta into the medium. Thus this mutant betaAPP may cause AD because its processing is altered in a way that releases increased amounts of Abeta.