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Open Access Research article

Modeling of chemical inhibition from amyloid protein aggregation kinetics

José Antonio Vázquez

Author Affiliations

Grupo de Reciclado e Valorización de Residuos (REVAL), Instituto de Investigacións Mariñas (IIM-CSIC), C/ Eduardo Cabello 6, CP36208 Vigo, Spain

BMC Pharmacology and Toxicology 2014, 15:9  doi:10.1186/2050-6511-15-9

Published: 27 February 2014

Abstract

Backgrounds

The process of amyloid proteins aggregation causes several human neuropathologies. In some cases, e.g. fibrillar deposits of insulin, the problems are generated in the processes of production and purification of protein and in the pump devices or injectable preparations for diabetics. Experimental kinetics and adequate modelling of chemical inhibition from amyloid aggregation are of practical importance in order to study the viable processing, formulation and storage as well as to predict and optimize the best conditions to reduce the effect of protein nucleation.

Results

In this manuscript, experimental data of insulin, Aβ42 amyloid protein and apomyoglobin fibrillation from recent bibliography were selected to evaluate the capability of a bivariate sigmoid equation to model them. The mathematical functions (logistic combined with Weibull equation) were used in reparameterized form and the effect of inhibitor concentrations on kinetic parameters from logistic equation were perfectly defined and explained. The surfaces of data were accurately described by proposed model and the presented analysis characterized the inhibitory influence on the protein aggregation by several chemicals. Discrimination between true and apparent inhibitors was also confirmed by the bivariate equation. EGCG for insulin (working at pH = 7.4/T = 37°C) and taiwaniaflavone for Aβ42 were the compounds studied that shown the greatest inhibition capacity.

Conclusions

An accurate, simple and effective model to investigate the inhibition of chemicals on amyloid protein aggregation has been developed. The equation could be useful for the clear quantification of inhibitor potential of chemicals and rigorous comparison among them.

Keywords:
Protein fibrillation kinetics; Mathematical modeling; Sigmoid bivariate equation