Investigating whether suppressing the DNA damage response is neuroprotective in Drosophila models of C9orf72 ALS-FTD

Butler, Lauren (2024). Investigating whether suppressing the DNA damage response is neuroprotective in Drosophila models of C9orf72 ALS-FTD. University of Birmingham. M.Sc.

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Abstract

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases that have a clear genetic overlap. The most common cause of both is a hexanucleotide repeat expansion in the C9orf72 gene. This has the ability to cause genomic instability and DNA damage. DNA damage is a key feature of many neurodegenerative diseases. Accumulation of double strand DNA breaks leads to chronic activation of the DNA damage response (DDR) and neurodegeneration. Previous work has shown that inhibiting DDR proteins, including ataxia-telangiectasia-mutated kinase (ATM) and checkpoint kinase 2 (Chk2), in a Drosophila Alzheimer’s disease model was neuroprotective. In this project I investigated whether similar knockdown of DDR proteins would also be neuroprotective in a Drosophila ALS-FTD model. I have shown that knockdown of ATM improved the survival rate of my Drosophila ALS-FTD model but produced inconsistent results on its effect on the motor function decline. Repetition of the motor function experiments would be required to give a definitive result.

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):