The self-assembly of proteins and peptides into fibrillar and oligomeric aggregates is linked to several devastating neurodegenerative diseases. In our studies, we seek to understand the equilibrium and kinetics of amyloid formation including the reaction mechanisms and molecular driving forces. We take as a starting point ultra-pure peptide in a defined buffer system devoid of cosolvents or mechanical insults to derive quantitative values for parameters related to solubility (equilibrium), nucleation rates (kinetics), and the microscopic steps underlying the process (mechanism). Then, by introducing various factors ranging from small ions to entire body fluids, and by varying the temperature we can start to approach the energy barriers and molecular driving forces for the process, as well as the role of aggregation enhancers and inhibitors. The ultimate goal is to provide a physicochemical basis for the development of therapeutic strategies for Alzheimer, Parkinson and related diseases.

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