Introduction
Amyloid-forming peptides and proteins underlie or are involved in
devastating diseases including Alzheimer’s, Parkinson’s, Type 2
diabetes, and Creutzfeldt-Jakob (Mad Cow’s), and some cancers. Analyses
of their structures, functions, and dysfunctions pose complicated
problems that are difficult to solve. Amyloids are shape-shifters with a
substantial amount of disorder. They adopt a plethora of secondary
structures, conformations, and assemblies, these are often present
simultaneously in dynamic equilibrium and depend upon numerous factors;
e.g., peptide and salt concentrations, time, cofactors,
post-translational modifications, and initial structure (seeds).
α-Synuclein (α-Syn), a contributor to Parkinson’s Disease (PD), is a
prime example (for recent review see Meade et al. [1]). Studies by
Cremades et al. [2] illustrated the variance in oligomer sizes and
how they alter as a function of time (Fig. 1). Similar results were
obtained for the dissociation of fibrils into oligomers, demonstrating
the dynamic nature of transitions among numerous semi-stable assemblies.