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.

journal_name

Math Biosci

journal_title

Mathematical biosciences

authors

Kuznetsov IA,Kuznetsov AV

doi

10.1016/j.mbs.2016.05.002

subject

Has Abstract

pub_date

2016-08-01 00:00:00

pages

22-9

eissn

0025-5564

issn

1879-3134

pii

S0025-5564(16)30048-7

journal_volume

278

pub_type

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