Norstrom Eric
Department of Biological Sciences, Neuroscience Program, DePaul University, Chicago, IL 60614, USA.
Discov Med. 2017 Apr;23(127):269-276.
Alzheimer's disease (AD) continues to be a daunting and costly challenge for research, medicine, and society. AD pathologies point toward the involvement of metabolic fragments of the amyloid precursor protein (APP) in the pathogenesis of the disease. Through sequential enzymatic processing, APP is metabolized into several potential polypeptides, including the toxic amyloid-β (Aβ) peptide. Though great progress has been made in understanding the mechanism of conventional metabolic processing of APP to yield products such as Aβ, AD remains unpreventable and irreversible at any stage. Recent new reports provide data that add both complexity to the issue and new hope for potential avenues of therapeutic intervention. Novel metabolic processing events such as delta-secretase and eta-secretase have been revealed that generate previously uncharacterized APP metabolic fragments with the potential to participate in AD pathogenesis. Additionally, enzymes known to act in other metabolic pathways, such as meprin β, have been found to cleave APP to yield products known to participate in AD pathologies. This review provides an overview of current knowledge of conventional and novel APP processing.
阿尔茨海默病（AD）对于科研、医学和社会而言，仍然是一项艰巨且代价高昂的挑战。AD的病理学研究表明，淀粉样前体蛋白（APP）的代谢片段参与了该疾病的发病机制。通过一系列酶促加工过程，APP被代谢为几种潜在的多肽，包括有毒的淀粉样β（Aβ）肽。尽管在理解APP常规代谢加工以产生诸如Aβ等产物的机制方面已经取得了很大进展，但AD在任何阶段仍然无法预防且不可逆转。最近的新报告提供的数据既增加了该问题的复杂性，也为潜在的治疗干预途径带来了新希望。已揭示了诸如δ-分泌酶和η-分泌酶等新型代谢加工事件，这些事件产生了以前未被表征的APP代谢片段，它们有可能参与AD的发病机制。此外，已发现已知在其他代谢途径中起作用的酶，如膜金属蛋白酶β，可切割APP以产生已知参与AD病理学的产物。本综述概述了目前关于常规和新型APP加工的知识。
