Mechanism of tau R3 aggregation and inhibition revealed by NMR-based chemical kinetics

Protein misfolding diseases are becoming increasingly prevalent with the increase in life expectancy and lifestyle changes over the last century, and constitute a health challenge at a global level. Macroscopic protein deposits of amyloids are associated with diseases such as Alzheimer’s (tau and β-amyloid) and Parkinson’s (α-synuclein). The mechanisms of protein aggregation are poorly understood, and such knowledge would enable the rational design of therapeutics for these diseases. Several key chemical processes have been proposed; chemical kinetics approaches can be applied to test such models, but are limited by the information content and reproducibility of the data.