A mathematical model of redox/methylation metabolism in human neuronal cells

Permanent URL: http://hdl.handle.net/2047/d20004840
Title:
A mathematical model of redox/methylation metabolism in human neuronal cells
Creator:
Kesir, Mustafa (Author)
Contributor:
Malioutov, Mikhail (Advisor)
Deth, Richard C. (Committee member)
Reed, Michael C. (Committee member)
Ding, Aidong (Committee member)
Sadaka, Hanai (Committee member)
Publisher:
Boston, Massachusetts : Northeastern University, 2013
Date Accepted:
December 2013
Date Awarded:
January 2014
Type of resource:
Text
Genre:
Dissertations
Format:
electronic
Digital origin:
born digital
Abstract/Description:
It is vital for cells to control their state of reduction and oxidation (redox), and the metabolic pathways providing this crucial function intersect with pathways controlling hundreds of methylation reactions. It has been hypothesized that abnormal redox and methylation status contributes to a number of brain disorders, including autism or Alzheimer's disease (AD). Following in the footsteps of Reed et al., who created a mathematical model of these pathways in liver cells, I built a mathematical model of redox and methylation metabolism for human neuronal cells, in order to explore the predictions of this hypothesis and to see if further insights can be gained based on this model. While redox and methylation metabolism exists in all human cells, in many regards the brain compartment provides a unique environment for its many aspects of regulation.

Among other findings, simulations with this neuronal model support the hypothesis that inhibition of selenoenzymes by mercury can alter the redox status of the cell to a significant extent, which can ultimately contribute to autism or AD, depending on age. In addition, inhibition of these enzymes could be essentially irreversible, in the sense that, no other treatment could restore the levels of key metabolites back to normal homeostatic levels. We further use the model to explore the behavior of neuronal cells under different metabolic circumstances.
Subjects and keywords:
Autism
Alzheir's Disease
EAAT3
Mathematical Model
Neuronal Cells
SH-SY5Y cells
Applied Mathematics
Mathematics
DOI:
https://doi.org/10.17760/d20004840
Permanent Link:
http://hdl.handle.net/2047/d20004840
Use and reproduction:
In Copyright: This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the right-holder(s). (http://rightsstatements.org/vocab/InC/1.0/)
Copyright restrictions may apply.

Downloads