α- and β-secretase:: profound changes in Alzheimer's disease
α- and β-secretase:: profound changes in Alzheimer's disease
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DOI：
10.1016/s0006-291x(02)02635-9
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发表时间：
2002-12-06
影响因子：
3.1
通讯作者：
Allen, SJ
中科院分区：
文献类型：
--
作者：
Tyler, SJ;Dawbarn, D;Allen, SJ
淀粉样斑块是阿尔茨海默病的神经病理标志，由β-淀粉样蛋白(Abeta)沉积产生，β-淀粉样蛋白前体蛋白(APP)被β-分泌酶分解。在正常大脑中只有少量的Abeta形成；更典型的情况是，这是由α-分泌酶处理APP所排除的。在这里，我们描述了散发性阿尔茨海默病颞叶皮质中α-分泌酶的减少(正常的81%)和β-分泌酶活性的大幅增加(185%)。由于阿尔茨海默病的阿尔法分泌酶主要存在于已知的易患阿尔茨海默病的神经元中，而且已知阿尔茨海默病的阿尔法和β分泌酶之间存在底物APP之间的竞争，因此这里测试的大多数阿尔茨海默病样本中的α-分泌酶含量都很低，这一点很重要。在接受检查的阿尔茨海默病患者中，有80%的人β-分泌酶增加，α-分泌酶减少，或两者兼而有之；这可能解释了大多数人患上阿尔茨海默氏症的原因。(C)2002年埃尔塞维尔科学公司(美国)。版权所有。
The amyloid plaque, a neuropathological hallmark of Alzheimer's disease, is produced by the deposition of beta-amyloid (Abeta) peptide, which is cleaved from Amyloid Precursor Protein (APP) by the enzyme beta-secretase. Only small amounts of Abeta form in normal brain; more typically this is precluded by the processing of APP by alpha-secretase. Here, we describe a decrease in alpha-secretase (81% of normal) and a large increase in beta-secretase activity (185%) in sporadic Alzheimer's disease temporal cortex. Since alpha-secretase is present principally in neurons known to be vulnerable in Alzheimer's disease, and there is known competition between alpha- and beta-secretase for the substrate APP, it is significant that the majority of Alzheimer samples tested here were low in a-secretase. Eighty percent of Alzheimer brains examined had an increase in beta-secretase, a decrease in alpha-secretase, or both; which may account for the means by which the majority of people develop Alzheimer's disease. (C) 2002 Elsevier Science (USA). All rights reserved.