Hébert Sébastien S, Bourdages Valérie, Godin Chantal, Ferland Mélissa, Carreau Madeleine, Lévesque Georges
Molecular and Human Genetics Unit, CHUQ-Pavillon St-François d'Assise, 10 rue de 1' Espinay, G1L 3L5, Québec, Canada.
Neurobiol Dis. 2003 Aug;13(3):238-45. doi: 10.1016/s0969-9961(03)00035-4.
A neuropathological hallmark of Alzheimer's disease is the presence of amyloid plaques. The major constituent of these plaques, occurring largely in brain areas important for memory and cognition, is the 40-42 amyloid residues (Abeta). Abeta is derived from the amyloid protein precursor after cleavage by the recently identified beta-secretase (BACE1) and the putative gamma-secretase complex containing presenilin 1 (PS1). In an attempt to develop a functional secretase enzymatic assay in yeast we demonstrate a direct binding between BACE1 and PS1. This interaction was confirmed in vivo using coimmunoprecipitation and colocalization studies in human cultured cells. Our results show that PS1 preferably binds immature BACE1, thus possibly acting as a functional regulator of BACE1 maturation and/or activity.
阿尔茨海默病的一个神经病理学特征是存在淀粉样斑块。这些斑块的主要成分是40 - 42个淀粉样残基（β淀粉样蛋白），主要出现在对记忆和认知至关重要的脑区。β淀粉样蛋白是由淀粉样蛋白前体在被最近鉴定出的β分泌酶（BACE1）和包含早老素1（PS1）的假定γ分泌酶复合物切割后产生的。为了在酵母中开发一种功能性分泌酶酶活性测定方法，我们证明了BACE1和PS1之间存在直接结合。这种相互作用在人体培养细胞中通过免疫共沉淀和共定位研究在体内得到了证实。我们的结果表明，PS1优先结合未成熟的BACE1，因此可能作为BACE1成熟和/或活性的功能调节剂。
