Modeling the Aggregation of Interacting Neurofilaments in the Axon

Download or read book Modeling the Aggregation of Interacting Neurofilaments in the Axon written by Susan J. Foss and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: An axon is a long, thin projection away from a neuron. Axonal transport, a crucial process for the survival of a neuron, is the transport of various organelles and proteins along microtubules, which act as an intracellular highway. Disruptions of axonal transport is associated with many neurodegenerative disorders such as motor neuron diseases (including ALS), Alzheimer's disease, and Huntington's disease. In these diseases, we frequently observe local accumulations of cargoes, which resemble highway traffic jams with pileups of cars. It has been hypothesized that these diseases result from "intracellular traffic jams" caused by the interactions of cargoes. In this thesis, we test this hypothesis using a stochastic model that describes cargoes as interacting particles that switch between different moving and pausing states. Specifically, we apply this model to the transport of neurofilaments. Our results suggest that, although the model can generate traffic jams under certain parameter regimes, these jams may be fundamentally different from those observed in diseases. Another conclusion of this model is that low processivity of the molecular motors that transport neurofilaments help avoid intracellular jams. This explains the evolutionary question, "why is the system is designed this way?".