PRODUCTION OF THE ALZHEIMER AMYLOID-BETA PROTEIN BY NORMAL PROTEOLYTIC PROCESSING
PRODUCTION OF THE ALZHEIMER AMYLOID-BETA PROTEIN BY NORMAL PROTEOLYTIC PROCESSING
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DOI：
10.1126/science.1439760
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发表时间：
1992-10-02
期刊：
影响因子：
56.9
通讯作者：
YOUNKIN, SG
中科院分区：
文献类型：
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作者：
SHOJI, M;GOLDE, TE;YOUNKIN, SG
4 千道尔顿（39 至 43 个氨基酸）淀粉样β 蛋白 (betaAP) 以淀粉样蛋白形式沉积在阿尔茨海默病患者的大脑中，源自一种大蛋白质，即淀粉样β 蛋白前体 (betaAPP)。表达带有βAP、羧基末端βAPP衍生物的人单核白血病（K562）细胞释放大量可溶性4千道尔顿βAPP衍生物，与阿尔茨海默病中沉积的βAP基本相同。用表达全长 betaAPP 的构建体和仅表达内源 betaAPP 的 M17 细胞转染的人神经母细胞瘤 (M17) 细胞也释放可溶性 4 千道尔顿 betaAP，并且在阿尔茨海默氏病个体和正常个体的脑脊液中很容易检测到相似的（如果不是相同的）片段。因此，细胞通常产生并释放可溶性 4 千道尔顿 betaAP，其与阿尔茨海默氏病中作为不溶性淀粉样原纤维沉积的 4 千道尔顿 betaAP 基本相同。
The 4-kilodalton (39 to 43 amino acids) amyloid beta protein (betaAP), which is deposited as amyloid in the brains of patients with Alzheimer's disease, is derived from a large protein, the amyloid beta protein precursor (betaAPP). Human mononuclear leukemic (K562) cells expressing a betaAP-bearing, carboxyl-terminal betaAPP derivative released significant amounts of a soluble 4-kilodalton betaAPP derivative essentially identical to the betaAP deposited in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing full-length betaAPP and M17 cells expressing only endogenous betaAPP also released soluble 4-kilodalton betaAP, and a similar, if not identical, fragment was readily detected in cerebrospinal fluid from individuals with Alzheimer's disease and normal individuals. Thus cells normally produce and release soluble 4-kilodalton betaAP that is essentially identical to the 4-kilodalton betaAP deposited as insoluble amyloid fibrils in Alzheimer's disease.