Crespo2012 - Kinetics of Amyloid Fibril Formation

  public model
Short description
Crespo2012 - Kinetics of Amyloid Fibril Formation

This model is described in the article:

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.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L2V4)
Related Publication
  • A generic crystallization-like model that describes the kinetics of amyloid fibril formation.
  • Crespo R, Rocha FA, Damas AM, Martins PM
  • The Journal of biological chemistry , 8/ 2012 , Volume 287 , pages: 30585-30594
  • LEPAE, Laborat√≥rio de Engenharia de Processos Ambiente e Energia, Departamento de Engenharia Qu√≠mica, Faculdade de Engenharia, Universidade do Porto, 4200-465 Porto, Portugal.
  • 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.
Contributors
Audald Lloret i Villas, administrator

Metadata information

is
BioModels Database MODEL1407170000
BioModels Database BIOMD0000000531
isDescribedBy
PubMed 22767606
hasTaxon
Taxonomy Homo sapiens
isVersionOf
hasProperty
Human Disease Ontology Alzheimer's disease
Curation status
Curated
Name Description Size Actions

Model files

BIOMD0000000531_url.xml SBML L2V4 representation of Crespo2012 - Kinetics of Amyloid Fibril Formation 13.40 KB Preview | Download

Additional files

BIOMD0000000531.xpp Auto-generated XPP file 1.14 KB Preview | Download
BIOMD0000000531.svg Auto-generated Reaction graph (SVG) 851.00 bytes Preview | Download
BIOMD0000000531.pdf Auto-generated PDF file 131.87 KB Preview | Download
BIOMD0000000531.sci Auto-generated Scilab file 154.00 bytes Preview | Download
BIOMD0000000531-biopax2.owl Auto-generated BioPAX (Level 2) 4.61 KB Preview | Download
BIOMD0000000531.m Auto-generated Octave file 1.92 KB Preview | Download
BIOMD0000000531-biopax3.owl Auto-generated BioPAX (Level 3) 4.80 KB Preview | Download
model.cps Copasi file of the model 25.46 KB Preview | Download
BIOMD0000000531.png Auto-generated Reaction graph (PNG) 5.04 KB Preview | Download
BIOMD0000000531_urn.xml Auto-generated SBML file with URNs 13.27 KB Preview | Download
BIOMD0000000531.vcml Auto-generated VCML file 15.41 KB Preview | Download

  • Model originally submitted by : Audald Lloret i Villas
  • Submitted: Jul 17, 2014 5:00:32 PM
  • Last Modified: Dec 21, 2018 5:24:18 PM
Revisions
  • Version: 3 public model Download this version
    • Submitted on: Dec 21, 2018 5:24:18 PM
    • Submitted by: administrator
    • With comment: Include the additional files provided by the submitter in the original submission: model.cps
  • Version: 2 public model Download this version
    • Submitted on: Sep 9, 2014 1:49:05 PM
    • Submitted by: Audald Lloret i Villas
    • With comment: Current version of Crespo2012 - Kinetics of Amyloid Fibril Formation
  • Version: 1 public model Download this version
    • Submitted on: Jul 17, 2014 5:00:32 PM
    • Submitted by: Audald Lloret i Villas
    • With comment: Original import of Crespo2012 - Kinetics of Amyloid Fibril Formation
Curator's comment:
(added: 17 Jul 2014, 18:09:42, updated: 17 Jul 2014, 18:09:42)
Figure 3 of the reference publication has been reproduced here. The simulation was carried out using Copasi v4.12 (Build 81) and the plot was generated using Gnuplot.