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 Bioscijournal_title
Mathematical biosciencesauthors
Kuznetsov IA,Kuznetsov AVdoi
10.1016/j.mbs.2016.05.002subject
Has Abstractpub_date
2016-08-01 00:00:00pages
22-9eissn
0025-5564issn
1879-3134pii
S0025-5564(16)30048-7journal_volume
278pub_type
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