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Identification of biomarkers for MND, and understanding the potential role of the cyanotoxin BMAA in neurodegeneration

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thesis
posted on 28.03.2022, 22:45 authored by Vanessa Tan
Motor Neuron Disease (MND) or Amyotrophic Lateral Sclerosis (ALS) is a devastating neurological disease with no biological diagnostic markers, no effective treatment, and no cure. We investigate the immune related Kynurenine Pathway (KP) for a role in ALS. The production of neuroactive metabolites during the KP indicate that there is an overlap with the mechanisms of ALS, particularly with the neurotoxin quinolinic acid. Subsequently, we investigate the KP metabolome, analysing 10 metabolites using biochemical analyses including High Performance Liquid Chromatography and Gas Chromatography/Mass Spectrometry. Using serum from a longitudinal cohort of 66 ALS patients, we establish a potential for KP metabolomics to be used a biomarker for ALS. To increase specificity and reliability of these results, in collaboration with Macquarie University Neurology, we established a Neurodegenerative Diseases Biobank to collect patient biological samples. These samples would facilitate future investigations into the mechanisms, genetics, biomarkers, and to detect the presence of toxic compounds such as metals, or β-methylamino-L-alanine (BMAA). We describe the establishment of the biobank as a case study for future references. BMAA is known to be neurotoxic, and we investigate its role ALS. We reveal its role in promoting axonal degeneration and neuronal death, and show for the first time, its ability to spread transcellularly -- abstract.

History

Table of Contents

Chapter 1: KP and MND -- Chapter 2: Case study -- Chapter 3: BMAA & Neurotoxicity -- Chapter 4: Other publications arising from the candidature.

Notes

Contains bibliographical references Thesis by publication.

Awarding Institution

Macquarie University

Degree Type

Thesis PhD

Degree

PhD (Advanced Medicine), Macquarie University, Faculty of Medicine and Health Sciences, Department of Biomedical Sciences, Centre for Motor Neuron Disease Research

Department, Centre or School

Department of Biomedical Sciences

Year of Award

2017

Principal Supervisor

Gilles J. Guillemin

Rights

Copyright Vanessa Tan 2017. Copyright disclaimer: http://mq.edu.au/library/copyright

Language

English

Extent

1 online resource (xvi, 242 pages) illustrations

Former Identifiers

mq:71826 http://hdl.handle.net/1959.14/1278499