Hubin Ellen, Cioffi Federica, Rozenski Jef, van Nuland Nico A J, Broersen Kerensa
Nanobiophysics Group, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, Universiteit Twente, Enschede, The Netherlands; Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium; Structural Biology Research Center, VIB, Pleinlaan 2, 1050 Brussels, Belgium.
Nanobiophysics Group, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, Universiteit Twente, Enschede, The Netherlands.
Biochim Biophys Acta. 2016 Jun;1860(6):1281-90. doi: 10.1016/j.bbagen.2016.03.010. Epub 2016 Mar 8.
To enhance our understanding of the potential therapeutic utility of insulin-degrading enzyme (IDE) in Alzheimer's disease (AD), we studied in vitro IDE-mediated degradation of different amyloid-beta (Aβ) peptide aggregation states. Our findings show that IDE activity is driven by the dynamic equilibrium between Aβ monomers and higher ordered aggregates. We identify Met(35)-Val(36) as a novel IDE cleavage site in the Aβ sequence and show that Aβ fragments resulting from IDE cleavage form non-toxic amorphous aggregates. These findings need to be taken into account in therapeutic strategies designed to increase Aβ clearance in AD patients by modulating IDE activity.
为了增强我们对胰岛素降解酶（IDE）在阿尔茨海默病（AD）中潜在治疗效用的理解，我们研究了体外IDE介导的不同淀粉样β（Aβ）肽聚集状态的降解情况。我们的研究结果表明，IDE活性由Aβ单体与更高阶聚集体之间的动态平衡驱动。我们确定Met(35)-Val(36)为Aβ序列中的一个新的IDE切割位点，并表明IDE切割产生的Aβ片段形成无毒的无定形聚集体。在旨在通过调节IDE活性来增加AD患者Aβ清除率的治疗策略中，需要考虑这些发现。
