An analysis of the mitochondrial fission factor Drp1 along with mitochondrial protection genes in drosophila models of Parkinson disease

Hasan, Azra (2021) An analysis of the mitochondrial fission factor Drp1 along with mitochondrial protection genes in drosophila models of Parkinson disease. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Parkinson disease (PD) is the second most common neurodegenerative disorder and is strongly associated with the accumulation of Lewy bodies and loss of dopaminergic (DA) neurons in the substantia nigra of brain. The pathophysiology includes bradykinesia, tremors, motor, autonomic and cognitive disorders. Mitochondrial dysfunction induced cellular stress and cell death is implicated as the cause of PD. Mitochondrial dysfunction causes unregulated mitochondrial dynamics (biogenesis to degradation), impaired metabolic functions, oxidative stress, loss of proteostasis and abnormal cell death. Drp1 is crucial in mitochondrial dynamics and other functions, including apoptosis and mitophagy. To analyze the implication of altering the protein which affects mitochondrial health, I altered the expression of mitochondrial fission gene, Drp1; the transcription regulator, Rbf; mitophagy regulators Pink1 and parkin, Bcl-2 family genes Buffy and Debcl, Insulin receptor signalling genes foxo and trbl and increased disease risk gene α- synuclein; in DA neurons of Drosophila. I found that the altered expression of these key genes can have a beneficial, intermediate, and detrimental effect on the health of DA neurons as determined by lifespan and locomotor functions. Furthermore, I found that the overexpression and inhibition of Drp1, which encodes a mitochondrial fission protein, could suppress various PD like phenotypes in Drosophila.

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