Disentangling the Amyloid Pathways: A Mechanistic Approach to Etiology

Amyloids are fibrillar protein aggregates associated with diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), type II diabetes and Creutzfeldt–Jakob disease. The process of amyloid polymerization involves three pathological protein transformations; from natively folded conformation to the cross-β conformation, from biophysically soluble to insoluble, and from biologically functional to non-functional. While amyloids share a similar cross-β conformation, the biophysical transformation can either take place spontaneously via a homogeneous nucleation mechanism (HON) or catalytically on an exogenous surface via a heterogeneous nucleation mechanism (HEN). Here, we postulate that…