Parkinson Disease (PD) is a progressive neurodegenerative disorder characterized by the gradual loss of motor control and cognitive functions. These symptoms, resulting from the breakdown of dopaminergic neurons, often present in mid-late life and may lead to premature death. A number of molecular pathways have been implicated in the progression of Parkinson Disease to provide a variety of treatment options that offer temporary relief from disease symptoms. The search for preventative therapies and cures for the sporadic and inherited forms of the disease is ongoing.
A polymorphism in the Huntingtin Interacting Protein 1 related (Hip1r) gene in mammals has recently been associated with PD but its role in disease progression remains uncharacterized. Directed manipulation of the single Drosophila Hip1r homologue Hip1 in the dopaminergic neurons was carried out to provide an in vivo model of disease progression and symptom development. Investigation of motor ability and longevity of D. melanogaster upon overexpression and loss of function of Hip1 was completed. Motor analysis was examined by ranking the climbing ability of flies weekly in a glass vessel of regulated size and conditions. Longevity was analyzed by scoring experimental genotypes every two days for the presence of deceased individuals, beginning at day two post-eclosion and continuing until the death of all experimental samples. Directed expression of Hip1-RNAi in the dopaminergic neurons decreased the locomotor ability of the flies and increased the average lifespan. Overexpression of Hip1 in the dopaminergic neurons revealed the opposite effect, improving locomotor ability and slightly decreasing average lifespan. This suggests that a delicate balance of Hip1 exists in the dopaminergic neurons, and alteration of expression influences the motor ability and life expectancy of D. melanogaster. Maintaining a healthy balance of Hip1 in the dopaminergic neurons may offer a new therapeutic option for loss of locomotor ability and pre-mature death. Further investigation of Hip1r and its role in human disease progression is needed, and may be crucial to our understanding of PD, and perhaps Huntington Disease, in order to provide new therapeutic targets.
Funded by a School of Graduate Studies Fellowship to FAS and an NSERC Discovery Grant to BES.