Anoar, Sharifah Zahra Binti;
(2025)
Understanding Mitochondrial Dysfunction Linked to C9orf72 Hexanucleotide Repeat Expansion.
Doctoral thesis (Ph.D), UCL (University College London).
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Text (Thesis)
Anoar_10210539_thesis.pdf Access restricted to UCL open access staff until 1 July 2026. Download (3MB) |
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Text (Supplementary Information_1)
Sharifah Zahra Binti Anoar_supplemental files for Figure 3.8, Figure 3.9 and Figure 3.13.xlsx - Supplemental Material Access restricted to UCL open access staff until 1 July 2026. Download (270kB) |
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Text (Supplementary Information_2)
Sharifah Zahra Binti Anoar_supplemental files for the downregulated DEGs for C9 day 9.xlsx - Supplemental Material Access restricted to UCL open access staff until 1 July 2026. Download (493kB) |
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Text (Supplementary Information_3)
Sharifah Zahra Binti Anoar_supplemental files for the upregulated DEGs for C9 day 9.xlsx - Supplemental Material Access restricted to UCL open access staff until 1 July 2026. Download (435kB) |
Abstract
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are classified as neurodegenerative diseases. ALS primarily affects motor neurons, while FTD is characterised by a decline in cognitive functions. Although these diseases present distinct sets of symptoms, ALS and FTD represent two extremes of the same disease spectrum, with considerable overlap in genetic, clinical, and neuropathological features. Among these overlapping traits, mitochondrial dysfunction is associated with both conditions. Recent studies have shown that cells derived from patient-induced pluripotent stem cells (iPSCs) exhibit mitochondrial abnormalities, a phenomenon also observed in various animal disease models. A hexanucleotide repeat expansion in the C9orf72 (C9) gene is the most common genetic cause of both diseases and is linked to mitochondrial abnormalities. This project investigates mitochondrial dysfunction in a Drosophila C9 model and elucidates how mitochondrial genes influence C9 toxicity in adult Drosophila neurons. We have characterised mitochondrial physiology in our model and the transcriptional profile of mitochondrial genes. We find that genes related to mitochondrial function and mitochondrial copy number are downregulated in our model. Additionally, we have modulated key regulators of mitochondrial metabolism and show that we can partially rescue C9 toxicity.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Understanding Mitochondrial Dysfunction Linked to C9orf72 Hexanucleotide Repeat Expansion |
| Language: | English |
| Additional information: | Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10210539 |
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