Paul J. Barrett

TL;DR: NMR titration of C99 reveals a binding site for cholesterol, providing mechanistic insight into how cholesterol promotes amyloidogenesis and may aid in the design of Alzheimer’s therapeutics.

TL;DR: Binding of cholesterol to C99 appears to favor the amyloidogenic pathway in cells by promoting localization of C99 in lipid rafts, which may down-regulate ApoE-mediated cholesterol uptake and cholesterol biosynthesis.

TL;DR: The backbone dynamics of the substrate helix is investigated and it is found that the GlyGly hinge may precisely position the substrate within γ-secretase such that its catalytic center must start proteolysis at the known initial cleavage sites.

TL;DR: Recent advances in protein NMR that herald a renaissance in which a number of its most important applications reflect the broad problem-solving capability displayed by this method during its classical era during the 1970s and early 1980s are surveyed.

TL;DR: NMR results demonstrate a lack of specific binding of certain gamma-secretase modulators to monodisperse C99 in LMPG micelles, and indicate that C99 was likely to have been aggregated in some of the key experiments of the previous work and that binding of GSMs to these C99 aggregates is also of a nonspecific nature.