title: Mathematical models of α-synuclein transport in axons.
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).
authors.affiliation: a Department of Biomedical Engineering , Johns Hopkins University , Baltimore , MD 21218-2694 , USA.
authors.forename: I A
authors.initials: IA
authors.lastname: Kuznetsov
authors.affiliation: b Department of Mechanical and Aerospace Engineering , North Carolina State University , Raleigh , NC 27695-7910 , USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Kuznetsov
mesh_terms: D001370:Axonal Transport / Q000502:physiology*; D001369:Axons / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008962:Models, Theoretical; D010300:Parkinson Disease / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein
keywords: Parkinson's disease; diffusion; mathematical modeling; motor-driven transport; neuron; α-synuclein