A coupled model of fast axonal transport of organelles and slow axonal transport of tau protein

• Published in: Computer methods in biomechanics and biomedical engineering Vol. 18; no. 13; pp. 1485 - 1494
• Main Authors: Kuznetsov, I.A., Kuznetsov, A.V.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03.10.2015
• Subjects: Animals; Axonal Transport; Axons - metabolism; Computer Simulation; fast axonal transport; Humans; Kinesin - metabolism; Kinetics; Microtubules - metabolism; Models, Neurological; Neurons - physiology; organelle transport; Organelles; slow axonal transport; Synapses - physiology; tau protein; tau Proteins - metabolism; tau Proteins - physiology; fast axonal transport; slow axonal transport; organelle transport; tau protein
• DOI: 10.1080/10255842.2014.920830
• ISSN: 1025-5842; 1476-8259

We have developed a model that accounts for the effect of a non-uniform distribution of tau protein along the axon length on fast axonal transport of intracellular organelles. The tau distribution is simulated by using a slow axonal transport model; the numerically predicted tau distributions along the axon length were validated by comparing them with experimentally measured tau distributions reported in the literature. We then developed a fast axonal transport model for organelles that accounts for the reduction of kinesin attachment rate to microtubules by tau. We investigated organelle transport for two situations: (1) a uniform tau distribution and (2) a non-uniform tau distribution predicted by the slow axonal transport model. We found that non-uniform tau distributions observed in healthy axons (an increase in tau concentration towards the axon tip) result in a significant enhancement of organelle transport towards the synapse compared with the uniform tau distribution with the same average amount of tau. This suggests that tau may play the role of being an enhancer of organelle transport.