Amyloid formation as local environment-dependent process

Treatment for AD/PD should be based on three solutions: (1) preventing the formation of amyloid fibrils; (2) stopping the propagation of an existing fibril and (3) the potential fragmentation of an existing fibril. Proposals (the first two) for solving this problem at the molecular level are based on method using the analysis of the distribution of hydrophobicity in native proteins compared with this distribution in amyloid forms. This analysis is conducted using the fuzzy oil drop model (FOD-M). The approach based on the polarity/hydrophobicity relationship stems from the water-based environments present within a living organism, as water constitutes the fundamental environment in which proteins are active in living organisms. The main finding is in form of proposed solution for point 1 concerns the identification of factors that alter the characteristics of an aqueous environment acting as an external force field for folding proteins. The proposal for point 2 recalls the solution elaborated by evolution in the case of solenoid proteins using the short polypeptide chains preventing the unlimited propagation. The conclusions arising from the presented analysis lead to proposals for a series of experimental studies to confirm or reject the proposed solutions. The key question, however, is: Why does a fibril structure with unlimited potential for propagation form in the first place? An attempt to answer this question is postulated in this paper. The limitation of the presented model is that it operates on the known structures.