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BIOMD0000000548 - Sneppen2009 - Modeling proteasome dynamics in Parkinson's disease

 

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Reference Publication
Publication ID: 19411740
Sneppen K, Lizana L, Jensen MH, Pigolotti S, Otzen D.
Modeling proteasome dynamics in Parkinson's disease.
Phys Biol 2009; 6(3): 036005
Niels Bohr Institute, Copenhagen, Denmark. sneppen@nbi.dk  [more]
Model
Original Model: BIOMD0000000548.origin
Submitter: Audald Lloret i Villas
Submission ID: MODEL1409100000
Submission Date: 10 Sep 2014 10:39:23 UTC
Last Modification Date: 30 Oct 2014 13:25:26 UTC
Creation Date: 10 Sep 2014 12:17:58 UTC
Encoders:  Audald Lloret i Villas
set #1
bqbiol:isVersionOf Gene Ontology inclusion body assembly
Gene Ontology proteasome-mediated ubiquitin-dependent protein catabolic process
set #2
bqbiol:hasProperty Human Disease Ontology Parkinson's disease
set #3
bqbiol:hasTaxon Taxonomy Homo sapiens
Notes
Sneppen2009 - Modeling proteasome dynamics in Parkinson's disease

This model is described in the article:

Sneppen K, Lizana L, Jensen MH, Pigolotti S, Otzen D.
Phys Biol 2009; 6(3): 036005

Abstract:

In Parkinson's disease (PD), there is evidence that alpha-synuclein (alphaSN) aggregation is coupled to dysfunctional or overburdened protein quality control systems, in particular the ubiquitin-proteasome system. Here, we develop a simple dynamical model for the on-going conflict between alphaSN aggregation and the maintenance of a functional proteasome in the healthy cell, based on the premise that proteasomal activity can be titrated out by mature alphaSN fibrils and their protofilament precursors. In the presence of excess proteasomes the cell easily maintains homeostasis. However, when the ratio between the available proteasome and the alphaSN protofilaments is reduced below a threshold level, we predict a collapse of homeostasis and onset of oscillations in the proteasome concentration. Depleted proteasome opens for accumulation of oligomers. Our analysis suggests that the onset of PD is associated with a proteasome population that becomes occupied in periodic degradation of aggregates. This behavior is found to be the general state of a proteasome/chaperone system under pressure, and suggests new interpretations of other diseases where protein aggregation could stress elements of the protein quality control system.

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.

Model
Publication ID: 19411740 Submission Date: 10 Sep 2014 10:39:23 UTC Last Modification Date: 30 Oct 2014 13:25:26 UTC Creation Date: 10 Sep 2014 12:17:58 UTC
Mathematical expressions
Rules
Rate Rule (variable: F) Rate Rule (variable: P) Rate Rule (variable: C)  
Physical entities
Compartments Species
Brain F P C
Global parameters
m gamma nu sigma
Reactions (0)
Rules (3)
 
 Rate Rule (name: F) d [ F] / d t= m/(1+P)-gamma*F*P
 
 Rate Rule (name: P) d [ P] / d t= ((sigma-P)-gamma*F*P)+nu*C
 
 Rate Rule (name: C) d [ C] / d t= gamma*F*P-nu*C
 
 Brain Spatial dimensions: 3.0  Compartment size: 1.0
 
 F
Compartment: Brain
Initial concentration: 135.0
 
 P
Compartment: Brain
Initial concentration: 0.0
 
 C
Compartment: Brain
Initial concentration: 18.0
 
Global Parameters (4)
 
 m
Value: 25.0
Constant
 
 gamma
Value: 1.0
Constant
 
 nu
Value: 1.0
Constant
 
 sigma
Value: 1.0
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000548

Curator's comment: (updated: 10 Sep 2014 12:15:50 GMT)

Figure 3 of the reference publication has been reproduced here. Dynamics of proteasome (P), fibrils (F) and the complex (C) concentration are plotted during 150 arbitrary units.

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 the below link.

Additional file(s)
  • Sneppen2009 - Modeling proteasome dynamics in Parkinson's disease:
    Copasi file of the model
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