William P. Esler

TL;DR: In this paper, an affinity reagent designed to interact with the active site of γ-secretase was shown to be able to bind to heterodimeric forms of presenilins, polytopic proteins that are mutated in hereditary Alzheimer's.

TL;DR: Identification of the α-, β-, and γ-secretases provides potential targets for designing new drugs to treat Alzeheimer's disease.

TL;DR: The present study illustrates that the protein misfolding diseases are kinetically vulnerable to intervention and inhibiting the initial weak docking interaction between depositing Abeta and the template is a viable therapeutic target to prevent the critical conformational transition in the conversion of Abeta ((solution)) to Abeta((amyloid)) and thus prevent stable amyloid accumulation.

TL;DR: Results provide direct biochemical evidence that nicastrin is a member of the active γ-secretase complex, indicate that β-catenin, calsenilin, and presenil in-associated protein are not required for γ activity, and suggest an unprecedented mechanism of substrate–protease interaction.

TL;DR: It is reported here that an active congener, Aβ(10−35)-NH2, displays time dependence, pH−activity profile, and kinetic order of deposition similar to A β(1−40), and is sufficiently soluble for NMR spectroscopy in water under conditions where it actively deposits.