Article
Alzheimer's-Causing Mutations Shift Aβ Length by Destabilizing γ-Secretase-Aβn Interactions.
Cell - 27 Jul 2017
Szaruga Maria, Munteanu Bogdan, Lismont Sam, Veugelen Sarah, Horré Katrien, Mercken Marc, Saido Takaomi C, Ryan Natalie S, De Vos Tatjana, Savvides Savvas N, Gallardo Rodrigo, Schymkowitz Joost, Rousseau Frederic, Fox Nick C, Hopf Carsten, De Strooper Bart, Chávez-Gutiérrez Lucía
Abstract excerpt
Alzheimer's disease (AD)-linked mutations in Presenilins (PSEN) and the amyloid precursor protein (APP) lead to production of longer amyloidogenic Aβ peptides. The shift in Aβ length is fundamental to the disease; however, the underlying mechanism remains elusive. Here, we show that substrate shortening progressively destabilizes the consecutive enzyme-substrate (E-S) complexes that characterize the sequential...
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