Crespo2012 - Kinetics of Amyloid Fibril Formation

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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.

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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

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
  • Model originally submitted by : Audald Lloret i Villas
  • Submitted: 17-Jul-2014 17:00:32
  • Last Modified: 09-Sep-2014 13:49:05
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 09-Sep-2014 13:49:05
    • 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: 17-Jul-2014 17:00:32
    • 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.