The effects of altered expression of clueless on ageing and neurodegeneration in Drosophila melanogaster

Porter, Allison L. (2024) The effects of altered expression of clueless on ageing and neurodegeneration in Drosophila melanogaster. Masters thesis, Memorial University of Newfoundland.

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Abstract

Mitochondrial dysfunction is linked to the pathology of age-related and neurodegenerative disease, including Parkinson disease and amyotrophic lateral sclerosis. Preservation of mitochondrial function is determined by the interconnected processes governing mitochondrial homeostasis: fission, fusion, trafficking, mitophagy, and biogenesis. The Drosophila melanogaster protein Clueless and its mammalian homologue CLUH are cytoplasmic RNA-binding proteins essential for mitochondrial function that may influence all of these processes. Clueless and its homologues may act as master regulators of mitochondrial homeostasis to control these processes in response to environmental cues including stress-response signalling. The effects of altered expression of clueless in Drosophila melanogaster dopaminergic and motor neurons on ageing and neurodegeneration were examined through lifespan and climbing assays. In humans, dopaminergic neuron degeneration causes Parkinson disease, and motor neurons degeneration causes amyotrophic lateral sclerosis. Inhibited clueless expression in Drosophila melanogaster dopaminergic and motor neurons reduced early-life climbing ability, and inhibited clueless expression in motor neurons caused impaired lifespan and a more rapidly progressive loss of climbing ability with age. Inhibited expression of clueless in motor neurons therefore causes age-related disease in this model organism. RNAi-mediated clueless suppression in motor neurons is a promising novel model for investigation of the role of mitochondrial dysfunction in the pathology of amyotrophic lateral sclerosis.

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