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

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
(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.

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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

hasTaxon
Taxonomy Homo sapiens
isVersionOf
Gene Ontology inclusion body assembly
is
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