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A Nonlocal Model for the Segregation of Axonal Microtubules and Neurofilaments in Neurodegenerative Diseases

Toy, Jonathan Andrew
http://rave.ohiolink.edu/etdc/view?acc_num=osu1461080485

Abstract Details

2016, Master of Mathematical Sciences, Ohio State University, Mathematical Sciences.
Both the shape and function of an axon depend critically on the organization of its cytoskeleton, which is a dynamic system of intracellular polymers including microtubules, neurofilaments and actin microfilaments. Under normal conditions, microtubules and neurofilaments align longitudinally in axons and are interspersed in axonal cross-sections. However, in many neurodegenerative disorders, they separate radially with microtubules clustered centrally and neurofilaments located near the periphery. This striking polymer segregation proceeds to focal accumulations of neurofilaments and/or organelles that are early hallmarks of nerve degeneration. A recent stochastic model of the phenomena suggests that this segregation is a consequence of the disruptions of neurofilament transport along microtubules, and in the absence of neurofilament transport, axonal organelles pull microtubules to the center and displace neurofilaments to the periphery. Motivated by these results, we develop a nonlocal PDE model for the cross-sectional distribution of axonal microtubules and neurofilaments in this thesis, and use it to systematically analyze how different balances of organelle transport and neurofilament transport affect the cross-sectional organization of microtubules and neurofilaments. Results of the PDE model agree tightly with the results of the stochastic model and experimental data. Through modeling we highlight the importance of incorporating cargo interactions in addressing biological questions related to axonal transport.
Chuan Xue (Advisor)
Anthony Brown (Committee Member)
Joseph Tien (Committee Member)
74 p.
Mathematics
axon transport; microtubule; neurofilament; segregation; non-local; nonlocal; PDE

Recommended Citations

Citations

  • Toy, J. A. (2016). A Nonlocal Model for the Segregation of Axonal Microtubules and Neurofilaments in Neurodegenerative Diseases [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1461080485

    APA Style (7th edition)

  • Toy, Jonathan. A Nonlocal Model for the Segregation of Axonal Microtubules and Neurofilaments in Neurodegenerative Diseases. 2016. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1461080485.

    MLA Style (8th edition)

  • Toy, Jonathan. "A Nonlocal Model for the Segregation of Axonal Microtubules and Neurofilaments in Neurodegenerative Diseases." Master's thesis, Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1461080485

    Chicago Manual of Style (17th edition)

osu1461080485
533
© 2016, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.