Publication Date
8-2023
Date of Final Oral Examination (Defense)
6-14-2023
Type of Culminating Activity
Thesis
Degree Title
Master of Science in Biological Science
Department
Biology
Major Advisor
Brad Morrison, Ph.D.
Advisor
Eric Hayden, Ph.D.
Advisor
Cheryl Jorcyk, Ph.D.
Abstract
Parkinson’s Disease (PD) results from the loss of dopaminergic (DA) neurons within the substantia nigra. Current treatments attempt to replace the function of DA neurons instead of preventing their loss. Interleukin 13 receptor alpha 1 (IL13Ra1) was identified to be upregulated in PD. IL13Ra1 knockout mice were observed to be resistant to DA neuron loss under a chronic inflammation model. IL13Ra1 dimerizes with interleukin 4 receptor (IL4R) through the binding of either interleukin 4 (IL4) or interleukin 13 (IL13). In-silico screening was utilized to identify 40 low weight compounds that could target IL13Ra1-IL4R. To identify the drugs’ effects on IL4/IL13 signaling, an A549 cell line was treated with a drug and IL4/IL13 then pSTAT6 levels were quantified. Drug 4 and Drug 26 were observed robustly inhibiting IL4/IL13 signaling. Cytotoxicity was assessed using resazurin and lactate dehydrogenase survival assays. Drug 26 had observed cytotoxicity while Drug 4 had little to no observed cytotoxicity. Drug 4 was determined to be the lead drug for the remaining tests. Compounds structurally related to Drug 4 were also tested. We observed inhibitory effects on IL4/IL13 signaling testing with nicotine, niacin, and NAD. Our data suggests that Drug 4 is a promising nutraceutical candidate for future IL13Ra1 inhibition studies.
DOI
https://doi.org/10.18122/td.2126.boisestate
Recommended Citation
Pugel, Anton D., "IL13Ra1 Drug Discovery" (2023). Boise State University Theses and Dissertations. 2126.
https://doi.org/10.18122/td.2126.boisestate