Characterization of CG34126: the Drosophila melanogaster homologue of a novel Parkinson Disease gene

Saddika, Tarana (2019) Characterization of CG34126: the Drosophila melanogaster homologue of a novel Parkinson Disease gene. Masters thesis, Memorial University of Newfoundland.

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Abstract

Parkinson Disease (PD) is a progressive and debilitating neurodegenerative disease characterized by the inadequate function or the loss of dopamine-producing neurons in the human midbrain. PD has a complex etiology including aberrant protein inclusion, mitochondrial dysfunction, oxidative stress, and defects in protein trafficking, which may occur due to genetic or non-genetic factors. Recently identified PD causative genes can be evaluated in model organisms, through which pathophysiological interactions with previously discovered PD genes may be determined. A new gene associated with PD, UHRF1BP1L, has a putative role in mitochondrial dynamics and protein homeostasis, similar to several other well-established PD genes. I investigated CG34126, the only homologue of UHRF1BP1L in Drosophila melanogaster, in an attempt to model PD using the UAS-GAL4 system of inducible gene expression in the dopaminergic neurons as well as during the development of the eye. In brief, RNAi-mediated knockdown of CG34126 can reduce lifespan and locomotor ability over time, and the overexpression of CG34126 directed by the Dopa decarboxylase (Ddc)-Gal4 transgene leads to reduced longevity and climbing ability throughout life. However, overexpression of CG34126 partially rescues the parkin-RNA-interference model of PD by increasing both longevity and locomotor ability over time. No neurodevelopmental defect was observed through a detailed biometric analysis of eye phenotypes, either from overexpression or knockdown of CG34126. As the altered ectopic expression of CG34126 can either positively or negatively influence ageing and locomotion, the consequences of altering UHRF1BP1L function in the fly contributes a better understanding of PD and general ageing mechanisms.

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