Mathematical models of alpha-synuclein transport in axons

作者：Kuznetsov I A; Kuznetsov A V^*

来源：Computer Methods in Biomechanics and Biomedical Engineering, 2016, 19(5): 515-526.

DOI：10.1080/10255842.2015.1043628

• neuron
• alpha-synuclein
• motor-driven transport
• diffusion
• Parkinson's disease
• mathematical modeling

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

• 出版日期2016-4-3