Analysis of Ptp10D and Ptp4E during ageing and in Parkinson Disease models in Drosophila melanogaster

Abstract

Parkinson Disease (PD) is an age-dependent neurological disease that diminishes locomotory abilities. PD is the second most common neurodegenerative disease, after Alzheimer Disease (AD), with a lifetime risk of approximately one in 40 in human. The symptoms of PD include resting tremors, rigidity, and bradykinesia and are caused by a loss of dopaminergic neurons in the substantia nigra of the midbrain. Based upon a recent study, a group of novel candidate genes was discovered with the potential to influence PD etiology. Protein tyrosine phosphatase receptor type H (PTPRH) is one of the candidate genes with an established role in controlling mitochondrial morphology, which is a very important organelle in the development of PD. Importantly, PTPRH protein has roles in many cellular processes, including cell growth, the mitotic cycle, and differentiation. In the current study, Ptp10D and Ptp4E were identified as potential D. melanogaster homologues of PTPRH that are apparently the products of a gene duplication event. I show that PTPRH homologues in D. melanogaster have been conserved throughout evolution in vertebrates and invertebrates possessing a number of distinct conserved functional domains. Biometric, longevity, and climbing assays were performed to determine if altered expression of these genes could influence neurodevelopment, longevity and quality of life and/or produce novel models of PD. The individual inhibition of either Ptp10D or Ptp4E decreases the lifespan and locomotor ability over time. As well, directed loss of function has deleterious effects on neurodevelopment when inhibited in the compound eye. Interestingly, similar results were observed with regards to longevity, climbing over time, and eye biometric analyses when Ptp4E was overexpressed. In conclusion, altered expression of homologues of PTPRH in D. melanogaster, either ectopic overexpression or inhibition via RNAi, influences overall health and ageing to result in new potential models of PD.