Mathematical models of α-synuclein transport in axons

• Published in: Computer methods in biomechanics and biomedical engineering Vol. 19; no. 5; pp. 515 - 526
• Main Authors: Kuznetsov, I.A., Kuznetsov, A.V.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.04.2016
• Subjects: alpha-Synuclein - metabolism; Axonal Transport - physiology; Axons - metabolism; Axons - pathology; diffusion; Humans; mathematical modeling; Models, Theoretical; motor-driven transport; neuron; Parkinson Disease - pathology; Parkinson's disease; α-synuclein; mathematical modeling; neuron; diffusion; Parkinson's disease; motor-driven transport; α-synuclein
• DOI: 10.1080/10255842.2015.1043628
• ISSN: 1025-5842; 1476-8259

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).