Crespo2012 - Kinetics of Amyloid Fibril Formation

Crespo2012 - Kinetics of Amyloid Fibril
Formation

This model is described in the article:

A generic
crystallization-like model that describes the kinetics of
amyloid fibril formation.

Crespo R, Rocha FA, Damas AM,
Martins PM.
J. Biol. Chem. 2012 Aug; 287(36):
30585-30594
Abstract:

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 of 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 the
classic types of amyloid fibrillization kinetics identified in
our literature survey. Amyloid conversion represented as a
function of time is shown to follow different curve shapes,
ranging from sigmoidal to hyperbolic, according to the relative
importance of the nucleation and growth steps. Using the CLM,
apparently unrelated data are deconvoluted into generic
mechanistic information integrating the combined influence of
seeding, nucleation, growth, and fibril breakage events. It is
notable that this complex assembly of interdependent events is
ultimately reduced to a mathematically simple model, whose two
parameters can be determined by little more than visual
inspection. The good fitting results obtained for all cases
confirm the CLM as a good approximation to the generalized
underlying principle governing amyloid fibrillization. A
perspective is presented on possible applications of the CLM
during the development of new targets for amyloid disease
therapeutics.

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