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Mathematical models of α-synuclein transport in axons

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  • I.A. Kuznetsov
  • A.V. Kuznetsov

Abstract

To investigate possible effects of diffusion on α-synuclein (α-syn) transport in axons, we developed two models of α-syn transport, one that assumes that α-syn is transported only by active transport, as part of multiprotein complexes, and a second that assumes an interplay between motor-driven and diffusion-driven α-syn transport. By comparing predictions of the two models, we were able to investigate how diffusion could influence axonal transport of α-syn. The predictions obtained could be useful for future experimental work aimed at elucidating the mechanisms of axonal transport of α-syn. We also attempted to simulate possible defects in α-syn transport early in Parkinson's disease (PD). We assumed that in healthy axons α-syn localizes in the axon terminal while in diseased axons α-syn does not localize in the terminal (this was simulated by postulating a zero α-syn flux into the terminal). We found that our model of a diseased axon predicts the build-up of α-syn close to the axon terminal. This build-up could cause α-syn accumulation in Lewy bodies and the subsequent axonal death pattern observed in PD (‘dying back’ of axons).

Suggested Citation

  • I.A. Kuznetsov & A.V. Kuznetsov, 2016. "Mathematical models of α-synuclein transport in axons," Computer Methods in Biomechanics and Biomedical Engineering, Taylor & Francis Journals, vol. 19(5), pages 515-526, April.
    • Handle: RePEc:taf:gcmbxx:v:19:y:2016:i:5:p:515-526
    DOI: 10.1080/10255842.2015.1043628
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