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

Lisa Benecchi1, Jake Romley-Murias 1, Tiani Bello 1, Iris Farnum 1, Kayla Rendon-Torres 1, Lili Kosa 1, Ray Ball 1, Wayne Guida2, Denise B. Flaherty1

1Eckerd College, Biology and Chemistry Disciplines, Natural Sciences Collegium, St. Petersburg, Florida

2University of South Florida, Department of Chemistry, Tampa, Florida

While the adaptive immune system plays an essential role in infection response, the reality is that most organisms use innate immunity to defend themselves against infection and, overall, support inflammation pathways that keep cells healthy. Inflammatory responses can be triggered by pathogens or cell damage and are responsible for initiating the healing process by restoring tissue homeostasis. Parkinson’s disease (PD) is an example of a neurodegenerative disease for which inflammation is a hallmark of its pathology. It is characterized by the loss of dopaminergic neurons primarily caused by the aggregation of Lewy Bodies composed of a misfolded and aggregated alpha-synuclein (α-syn). The experiments presented here test the impact of chemical compounds to see if they bolster innate immune pathways in the model organism Caenorhabditis elegans. This was done by examining their effect on the transgenic expression of DAF-16::GFP and PMK-1::GFP, as well as their ability to reduce or exacerbate alpha-synuclein Lewy body aggregation and motility losses in a Parkinsonian model. Our data demonstrate that our compound “PZP” can upregulate DAF-16::GFP expression. Consistent with this finding, PZP also increases α-syn::YFP expression in our Parkins on’s model. This suggests that upregulation of DAF-16 can exacerbate alpha-synuclein-based pathology. In a longitudinal study, treatment with our compound “cxl”, showed a statistically significant preservation of motility in aged (12 days post egg lay) α-syn::YFP transgenic animals at a 10uM concentration. Furthermore, “cxl” also lowers α-syn::YFP expression in fluorescence intensity in Lewy Body aggregates at 10 nM to 10uM dosing at a statistically significant level. 

For more information, email: lbenecc@eckerd.edu

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