Vazquez2014 - Chemical inhibition from amyloid protein aggregation kinetics

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Vazquez2014 - Chemical inhibition from amyloid protein aggregation kinetics

This model is described in the article:

Vázquez JA.
BMC Pharmacol Toxicol 2014; 15(1): 9

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, A?42 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 A?42 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.

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Format
SBML (L2V4)
Related Publication
  • Modeling of chemical inhibition from amyloid protein aggregation kinetics.
  • Vázquez JA
  • BMC pharmacology & toxicology , 0/ 2014 , Volume 15 , pages: 9
  • Grupo de Reciclado e Valorización de Residuos (REVAL), Instituto de Investigacións Mariñas (IIM-CSIC), C/ Eduardo Cabello 6, CP36208 Vigo, Spain. jvazquez@iim.csic.es.
  • 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.
Contributors
Audald Lloret i Villas, administrator

Metadata information

is
BioModels Database MODEL1407300000
BioModels Database BIOMD0000000532
isDescribedBy
PubMed 24572069
hasTaxon
Taxonomy Homo sapiens
isVersionOf
hasProperty
Human Disease Ontology Alzheimer's disease
Curation status
Curated
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BIOMD0000000532_urn.xml Auto-generated SBML file with URNs 27.15 KB Preview | Download
Vazquez2014.cps Copasi file of the model 41.35 KB Preview | Download
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  • Model originally submitted by : Audald Lloret i Villas
  • Submitted: Jul 30, 2014 1:26:41 PM
  • Last Modified: Dec 21, 2018 5:24:21 PM
Revisions
  • Version: 3 public model Download this version
    • Submitted on: Dec 21, 2018 5:24:21 PM
    • Submitted by: administrator
    • With comment: Include the additional files provided by the submitter in the original submission: Vazquez2014.cps
  • Version: 2 public model Download this version
    • Submitted on: Sep 9, 2014 1:50:37 PM
    • Submitted by: Audald Lloret i Villas
    • With comment: Current version of Vazquez2014 - Chemical inhibition from amyloid protein aggregation kinetics
  • Version: 1 public model Download this version
    • Submitted on: Jul 30, 2014 1:26:41 PM
    • Submitted by: Audald Lloret i Villas
    • With comment: Original import of Vazquez2014 - Chemical inhibition from amyloid protein aggregation kinetics
Curator's comment:
(added: 30 Jul 2014, 17:34:56, updated: 30 Jul 2014, 17:34:56)
Figure 2A of the reference publication has been reproduced here, as two-dimensional plots whereas it is representation as a three-dimensional plot in the paper. Left: Simulation of Amyloid aggregation growth (X) with 1 mM chemical concentration for 20 hours time period. Right: Simulation of Amyloid aggregation growth (X) depending on varying concentrations of the inhibitor (C). The simulation was done using Copasi v4.12 (Build 81) and the plots were generated using Gnuplot. The Copasi file of the model with simulation settings can be downloaded from below link