Macquarie University
Browse

Investigating metabolic dysfunction in motor neuron disease

Download (3.72 MB)
thesis
posted on 2024-07-19, 03:32 authored by Alex Joseph Duff Johnson

Amyotrophic Lateral Sclerosis is an extremely devastating disease, with many pathological features which ultimately result in motor dysfunction and death. In search of therapeutic avenues, extensive investigation into these characteristics has revealed an overwhelming majority of cases presenting with one specific pathology – mutant TDP43. In addition to this, many metabolic side effects have been linked to ALS pathogenesis, including hypermetabolism – an increase in the use of energetic sources. Hypermetabolism along with many other metabolic defects result in further exacerbation of paralytic symptoms, and a decrease in survival time. To date, there exists no model that effectively produces both mutant TDP43 and significant metabolic issues, impeding the understanding of the role of TDP43 in metabolic dysfunction - hence halting development of therapeutic options. Previous work by colleagues has revealed that an inducible mouse model of TDP43 shows potential energetic defects, and as such warrants further investigation. Within my thesis, I characterise many aspects of the metabolic profile of iTDP43A315T mice, and further link them to TDP43 pathogenesis. I uncover glycogen storage dysregulation within these mice, alongside metabolic phenotypes similar to that of hypermetabolic ALS patients. As such, I investigate the link between neurodegenerative mechanisms and metabolic dysregulation within a mouse model of TDP43-based motor neuron disease and provide avenues for future research to take place within this field.

History

Table of Contents

1. Introduction -- 2. Methods -- 3. Results -- 4. Discussion -- 5. References -- Appendix

Awarding Institution

Macquarie University

Degree Type

Thesis MRes

Degree

Master of Research

Department, Centre or School

Macquarie Medical School

Year of Award

2024

Principal Supervisor

Fiona Bright

Additional Supervisor 1

Lars Ittner

Additional Supervisor 2

Annika van Hummel

Rights

Copyright: The Author Copyright disclaimer: https://www.mq.edu.au/copyright-disclaimer

Language

English

Extent

72 pages

Former Identifiers

AMIS ID: 342011

Usage metrics

    Macquarie University Theses

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC