The amyloid beta protein precursor mutations linked to familial Alzheimer's disease alter processing in a way that fosters amyloid deposition.
The amyloid beta protein precursor mutations linked to familial Alzheimer's disease alter processing in a way that fosters amyloid deposition.
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与家族性阿尔茨海默氏病相关的淀粉样蛋白前体突变以促进淀粉样蛋白沉积的方式改变加工过程。
DOI：
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发表时间：
1994
影响因子：
2.2
通讯作者：
S. Younkin
中科院分区：
文献类型：
--
作者：
S. Younkin
淀粉样β蛋白前体（BAPP）的正常加工导致可溶性4kD蛋白的分泌，所述可溶性4kD蛋白基本上与在阿尔茨海默病（AD）中形成不溶性纤维状沉积物的淀粉样β蛋白（A β）相同。淀粉样蛋白沉积在AD发生中起关键作用的有力证据来自于家族性AD（FAD）激酶的鉴定，其中AD表型与位于A β肽NH 2或COOH末端附近的β APP基因突变共分离。这些突变的位置立即表明，它们可能通过改变β APP加工的方式导致AD，这是淀粉样蛋白。在先前的研究中，我们发现表达NH 2侧突变体的转染细胞比表达野生型β APP或COOH侧突变体的细胞分泌多6倍的4 kD A β。我们现在已经表明，A β COOH侧的突变改变了加工过程，增加了更多淀粉样蛋白A β 1-42形式的分泌，这只占总4 kD A β产生的一小部分。因此，我们的数据表明，所有FAD相关的β APP突变改变β APP加工的方式，增加淀粉样蛋白形成的可能性。
Normal processing of the amyloid beta protein precursor (BAPP) results in secretion of a soluble 4 kD protein essentially identical to the amyloid beta protein (A beta) that forms insoluble fibrillar deposits in Alzheimer's disease (AD). Strong evidence that amyloid deposition plays a critical role in the development of AD has come from the identification of familial AD (FAD) kindreds in which the AD phenotype cosegregates with mutations in the beta APP gene that are located close to the NH2 or COOH end of the A beta peptide. The location of these mutations immediately suggests that they may cause AD by altering beta APP processing in a way that is amyloidogenic. In a previous study, we found that transfected cells expressing the NH2 side mutant secrete 6-fold more 4 kD A beta than those expressing wild type beta APP or COOH side mutants. We have now shown that the mutations on the COOH side of A beta alter processing to increase secretion of the more amyloidogenic A beta 1-42 form which constitutes only a small percentage of the total 4 kD A beta produced. Thus our data show that all of the FAD-linked beta APP mutations alter beta APP processing in a way that increases the likelihood of amyloid formation.
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影响因子：
56.9
作者：
SHOJI, M;GOLDE, TE;YOUNKIN, SG
通讯作者：
YOUNKIN, SG
影响因子：
56.9
作者：
SUZUKI, N;CHEUNG, TT;YOUNKIN, SG
通讯作者：
YOUNKIN, SG
影响因子：
56.9
作者：
MURRELL, J;FARLOW, M;BENSON, MD
通讯作者：
BENSON, MD
影响因子：
56.9
作者：
CAI, XD;GOLDE, TE;YOUNKIN, SG
通讯作者：
YOUNKIN, SG
影响因子：
2.9
作者：
JARRETT, JT;BERGER, EP;LANSBURY, PT
通讯作者：
LANSBURY, PT