SCREENING CXL FOR IMPACTS ON INNATE IMMUNITY AND INFLAMMATORY SIGNALING IN PARKINSON’S DISEASE IN C. ELEGANS

Abstract

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons primarily caused by the aggregation of Lewy bodies composed of misfolded α-synuclein proteins. We tested the impact of CXL, broadly categorized as an NSAID, to screen for efficacy as a therapeutic drug using Caenorhabditis elegans (C. elegans) daf-16::GFP, gst-4::GFP, and pmk-1::GFP innate immune signaling strains, as well as a Parkinsonian model (α-syn::YFP) to gauge its ability to modulate α-synuclein Lewy body aggregation and motility losses. In longitudinal studies, our data demonstrated statistically significant preservation of motility in day 12 post egg-lay α-syn::YFP transgenic animals at 10 µM concentration. Furthermore, daf-16::GFP transgenic animals showed a statistically significant decrease in fluorescence when exposed to 10 µM and 50 µM concentrations, gst-4::GFP transgenic animals showed a statistically significant decrease in fluorescence when exposed to 50 µM concentrations, and pmk-1::GFP transgenic animals showed a statistically significant decrease in fluorescence when exposed to 10 µM concentrations. This decreased fluorescence across all three strains suggests CXL may inhibit Lewy body aggregation. Despite these promising findings, results have been varied and more data is needed to fully assess the potential medical impact of CXL. 

For more information: cadamon@eckerd.edu