淀粉样前体蛋白（APP）和 BACE-1 的物理近似：阿尔茨海默病发病机制中的关键事件。
The physical approximation of APP and BACE-1: A key event in alzheimer's disease pathogenesis.
机构信息
Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, Wisconsin, 53705.
Department of Neuroscience, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, Wisconsin, 53705.
出版信息
Dev Neurobiol. 2018 Mar;78(3):340-347. doi: 10.1002/dneu.22556. Epub 2017 Nov 13.
Abstract
Alzheimer's disease (AD) is characterized by the accumulation of insoluble deposits of Amyloid β (Aβ) in brains. Aβ is derived by sequential cleavage of the amyloid precursor protein (APP) by β-site secretase enzyme (BACE-1) and γ-secretase. Proteolytic processing of APP by BACE-1 is the rate-limiting step in Aβ production, and this pathway is a prime target for AD drug development. Both APP and BACE-1 are membrane-spanning proteins, transported via secretory and endocytic pathways; and the physical interaction of APP and BACE-1 during trafficking is a key cell biological event initiating the amyloidogenic pathway. Here, we highlight recent research on intracellular trafficking/sorting of APP and BACE-1, and discuss how dysregulation of these pathways might lead to enhanced convergence of APP and BACE-1, and subsequent β-cleavage of APP. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 340-347, 2018.
摘要
阿尔茨海默病（AD）的特征是淀粉样β（Aβ）在大脑中不可溶沉积物的积累。Aβ是由β-分泌酶（BACE-1）和γ-分泌酶顺序切割淀粉样前体蛋白（APP）产生的。BACE-1 对 APP 的蛋白水解加工是 Aβ产生的限速步骤，该途径是 AD 药物开发的主要靶点。APP 和 BACE-1 都是跨膜蛋白，通过分泌和内吞途径运输；在运输过程中 APP 和 BACE-1 的物理相互作用是启动淀粉样途径的关键细胞生物学事件。在这里，我们强调 APP 和 BACE-1 的细胞内运输/分拣的最新研究，并讨论这些途径的失调如何导致 APP 和 BACE-1 的增强收敛，以及随后 APP 的β-切割。©2018 年 Wiley 期刊，Inc. 发展神经生物学 78:340-347，2018 年。
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