Kuznetsov2016(II) - α-syn aggregation kinetics in Parkinson's Disease

  public model
Short description
Kuznetsov2016(II) - α-syn aggregation kinetics in Parkinson's
This theoretical model uses 2-step Finke-Watzky (FW) kinetics
todescribe the production, misfolding, aggregation, transport and
degradation of α-syn that may lead to Parkinson's Disease
(PD). Deregulated α-syn degradation is predicted to be
crucialfor PD pathogenesis.
 
  

This model is described in the article:

Kuznetsov IA, Kuznetsov AV.
Math Biosci 2016 Aug; 278: 22-29

Abstract:

The aim of this paper is to develop a minimal model describing events leading to the onset of Parkinson's disease (PD). The model accounts for α-synuclein (α-syn) production in the soma, transport toward the synapse, misfolding, and aggregation. The production and aggregation of polymeric α-syn is simulated using a minimalistic 2-step Finke-Watzky model. We utilized the developed model to analyze what changes in a healthy neuron are likely to lead to the onset of α-syn aggregation. We checked the effects of interruption of α-syn transport toward the synapse, entry of misfolded (infectious) α-syn into the somatic and synaptic compartments, increasing the rate of α-syn synthesis in the soma, and failure of α-syn degradation machinery. Our model suggests that failure of α-syn degradation machinery is probably the most likely cause for the onset of α-syn aggregation leading to PD.

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 (L3V1)
Related Publication
  • What can trigger the onset of Parkinson's disease - A modeling study based on a compartmental model of α-synuclein transport and aggregation in neurons.
  • Kuznetsov IA, Kuznetsov AV
  • Mathematical biosciences , 8/ 2016 , Volume 278 , pages: 22-29
  • Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218-2694, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • The aim of this paper is to develop a minimal model describing events leading to the onset of Parkinson's disease (PD). The model accounts for α-synuclein (α-syn) production in the soma, transport toward the synapse, misfolding, and aggregation. The production and aggregation of polymeric α-syn is simulated using a minimalistic 2-step Finke-Watzky model. We utilized the developed model to analyze what changes in a healthy neuron are likely to lead to the onset of α-syn aggregation. We checked the effects of interruption of α-syn transport toward the synapse, entry of misfolded (infectious) α-syn into the somatic and synaptic compartments, increasing the rate of α-syn synthesis in the soma, and failure of α-syn degradation machinery. Our model suggests that failure of α-syn degradation machinery is probably the most likely cause for the onset of α-syn aggregation leading to PD.
Contributors
Thawfeek Varusai

Metadata information

hasTaxon
Taxonomy Homo sapiens
isVersionOf
Gene Ontology inclusion body assembly
isDescribedBy
hasProperty
Human Disease Ontology Parkinson's disease
Curation status
Curated
  • Model originally submitted by : Thawfeek Varusai
  • Submitted: Aug 15, 2016 1:52:21 PM
  • Last Modified: Dec 1, 2016 1:11:00 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Dec 1, 2016 1:11:00 PM
    • Submitted by: Thawfeek Varusai
    • With comment: Current version of Kuznetsov2016(II) - α-syn aggregation kinetics in Parkinson's Disease
  • Version: 1 public model Download this version
    • Submitted on: Aug 15, 2016 1:52:21 PM
    • Submitted by: Thawfeek Varusai
    • With comment: Original import of Kuznetsov2016(II) - α-syn aggregation kinetics in Parkinson's
Curator's comment:
(added: 15 Aug 2016, 16:08:19, updated: 15 Aug 2016, 16:08:19)
The model was encoded and simulated using Copasi 4.15. Wolfram Mathematica 8 and MS PowerPoint were used to process the figures. The difference between the two graphs is because of a change in a single parameter: first figure nA=2.91e-20 and second figure nA=0.