Using Drosophila melanogaster to model glial lipid biology dysfunction in Alzheimer’s disease

Seliverstov, Roman 2024. Using Drosophila melanogaster to model glial lipid biology dysfunction in Alzheimer’s disease. MPhil Thesis, Cardiff University. Item availability restricted.

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Abstract

Glial lipid accumulation in Alzheimer's disease (AD) has been known since the disease was first described in 1902, however remained a rather unexplored aspect of AD until recently. With recent advances in bioinformatics, the evidence of genetic involvement in lipid homeostasis dysfunction in AD became evident, with many significant risk-genes associated with lipid-related pathways. Newest findings suggest that some of these genes are tightly involved in lipid transport from neurons to glial cells, in response to AD pathology. Whilst carrying out an apparent neuroprotective role, this shuttling also appears to negatively affect glial ability to carry out their homeostatic functions. In the forefront of this research, Drosophila melanogaster, the fruit fly, emerged as a perfect model for studying the causality of this dysregulation. In this thesis we proposed and characterised a novel model of studying lipid droplet (LD) homeostasis dysfunction, by expressing a fluorescent marker for lipid droplets in fly wings. Fly wings contain both neurons and glia in close proximity, allowing to examine the interactions between these cell types, as well as are an easily accessible tissue. The glial wing LD model was shown to be responsive to axotomising injury and modifiable by neuronal debris phagocytosis modulation. Furthermore, the model has shown an increase in glial LDs in response to glial amyloid expression. Finally, the creation of a two-system expression model, allowing for independent expression of different transgenes in neurons and glia, led to a successful recreation of the glial LD accumulation in response to neuronal amyloid toxicity. Further development and utilisation of this model could provide a novel model of LD homeostasis examination. With growing evidence of lipid transport involvement in AD pathology, this model could allow for high-throughput phenotypic screening of AD risk genes, further unravelling this molecular hallmark of the disease.

Item Type:	Thesis (MPhil)
Date Type:	Completion
Status:	Unpublished
Schools:	Biosciences
Subjects:	Q Science > Q Science (General)
Date of First Compliant Deposit:	9 January 2025
Last Modified:	10 Jan 2025 11:40
URI:	https://orca.cardiff.ac.uk/id/eprint/175171

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