Fitting Neurological Protein Aggregation Kinetic Data via a 2-Step, Minimal/“Ockham's Razor” Model: The Finke−Watzky Mechanism of Nucleation Followed by Autocatalytic Surface Growth†

The aggregation of proteins has been hypothesized to be an underlying cause of many neurological disorders including Alzheimer's, Parkinson's, and Huntington's diseases; protein aggregation is also important to normal life function in cases such as G to F-actin, glutamate dehydrogenase, and tubulin and flagella formation. For this reason, the underlying mechanism of protein aggregation, and accompanying kinetic models for protein nucleation and growth (growth also being called elongation, polymerization, or fibrillation in the literature), have been investigated for more than 50 years. As a way to concisely present the key prior literature in the protein aggregation area, Table 1 in the main text summarizes 23 papers by 10 groups of authors that provide 5 basic classes of mechanisms for protein aggregation over the period from 1959 to 2007. However, and despite this major prior effort, still lacking are both (i) anything approaching a consensus mechanism (or mechanisms), and (ii) a generally useful, and t...