title: 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.
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.
authors.affiliation: Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218-2694, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: I A
authors.initials: IA
authors.lastname: Kuznetsov
authors.affiliation: Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910, USA. Electronic address: avkuznet@ncsu.edu.
authors.forename: A V
authors.initials: AV
authors.lastname: Kuznetsov
mesh_terms: D006801:Humans; D008959:Models, Neurological; D009474:Neurons / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein
keywords: Mathematical modeling; Multi-compartment model; Neuron; Parkinson's disease; α-synuclein