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

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Short description
This theoretical model uses 2-step Finke-Watzky (FW) kinetics to describe 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 crucial for PD pathogenesis.  
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

Curation status
Curated
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Model files

BIOMD0000000615.xml.origin SBML L3V1 representation of Kuznetsov2016(II) - α-syn aggregation kinetics in Parkinson\s Disease 50.94 KB Preview | Download

  • 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.