Math Biosci. 2016 Aug;278:22-9. doi: 10.1016/j.mbs.2016.05.002. Epub 2016 May 17.

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.

Author information

1: Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218-2694, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
2: Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910, USA. Electronic address: avkuznet@ncsu.edu.

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.