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BIOMD0000000531 - Crespo2012 - Kinetics of Amyloid Fibril Formation


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Reference Publication
Publication ID: 22767606
Crespo R, Rocha FA, Damas AM, Martins PM.
A generic crystallization-like model that describes the kinetics of amyloid fibril formation.
J. Biol. Chem. 2012 Aug; 287(36): 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.  [more]
Original Model: BIOMD0000000531.origin
Submitter: Audald Lloret i Villas
Submission ID: MODEL1407170000
Submission Date: 17 Jul 2014 17:00:32 UTC
Last Modification Date: 09 Sep 2014 13:49:05 UTC
Creation Date: 17 Jul 2014 18:11:16 UTC
Encoders:  Audald Lloret i Villas
set #1
bqbiol:isVersionOf Gene Ontology inclusion body assembly
Gene Ontology amyloid fibril formation
set #2
bqbiol:hasProperty Human Disease Ontology Alzheimer's disease
set #3
bqbiol:hasTaxon Taxonomy Homo sapiens
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


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.

Publication ID: 22767606 Submission Date: 17 Jul 2014 17:00:32 UTC Last Modification Date: 09 Sep 2014 13:49:05 UTC Creation Date: 17 Jul 2014 18:11:16 UTC
Mathematical expressions
Assignment Rule (variable: kat50) Assignment Rule (variable: v50t50) Assignment Rule (variable: alpha)  
Physical entities
Compartments Species
Cell alpha    
Global parameters
Ka kb kat50 v50t50
Reactions (0)
Rules (3)
 Assignment Rule (name: kat50) kat50 = ln(1/kb+1)
 Assignment Rule (name: v50t50) v50t50 = 1/4*(kb+1)*ln(1/kb+1)
 Assignment Rule (name: alpha) alpha = 1-1/(kb*(exp(Ka*time)-1)+1)
 Cell Spatial dimensions: 3.0  Compartment size: 1.0
Compartment: Cell
Initial concentration: 0.0
Global Parameters (4)
Value: 1.44
Value: 1.6E-10
Value: 22.5558473008547
Value: 5.63896182611591
Representative curation result(s)
Representative curation result(s) of BIOMD0000000531

Curator's comment: (updated: 17 Jul 2014 18:09:42 GMT)

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.

Additional file(s)
  • Crespo2012 - Kinetics of Amyloid Fibril Formation:
    Copasi file of the model