PLA2G6 Associated Neurodegeneration Modeled in Drosophila melanogaster

Abstract

PLA2G6 has been implicated as a locus for several neurodegenerative diseases. The PLA2G6 protein product is a phospholipase involved in phospholipid remodeling in cell membranes, regulating apoptosis, and cell signaling. A knockdown of the Drosophila melanogaster ortholog to PLA2G6 – CG6718 – results in phenotypes that model age-related neurodegenerative disease development in humans. Through the GAL4-UAS system, tissue specific knockdown of CG6718 can be achieved to determine in which cell types the PLA2G6 protein product is essential to maintain neuronal health with aging. Here, a climbing assay measuring the negative geotaxis response in Drosophila melanogaster with and without an RNAi knockdown in tyraminergic and octopaminergic neurons was performed to analyze whether PLA2G6 expressed in this neuronal subtype maintains health with aging. A statistically significant difference between the experimental control flies was observed at 20 days of age, suggesting that PLA2G6 is required in these neurons to prevent neurodegeneration during aging.