A Generic Crystallization-like Model That Describes the Kinetics of Amyloid Fibril Formation

摘要: Associated with neurodegenerative disorders such as Alzheimer, Parkinson, or prion diseases, the conversion of soluble proteins into amyloid fibrils remains poorly understood. Extensive "in vitro" measurements protein aggregation kinetics have been reported, but no consensus mechanism has emerged until now. This contribution aims at overcoming this gap by proposing a theoretically consistent crystallization-like model (CLM) that is able to describe classic types fibrillization identified in our literature survey. Amyloid represented function time shown follow different curve shapes, ranging from sigmoidal hyperbolic, according relative importance nucleation and growth steps. Using CLM, apparently unrelated data are deconvoluted generic mechanistic information integrating combined influence seeding, nucleation, growth, fibril breakage events. It notable complex assembly interdependent events ultimately reduced mathematically simple model, whose two parameters can be determined little more than visual inspection. The good fitting results obtained for all cases confirm CLM approximation generalized underlying principle governing fibrillization. A perspective presented on possible applications during development new targets disease therapeutics.