Graduation Date
6-2018
Document Type
Master's Thesis
Degree Name
Master of Science
Department or Program
Biological Sciences
Department or Program Chair
Meredith Protas, PhD
First Reader
Pankah Kapahi, PhD
Second Reader
Wolfgang Schweigkofler, PhD
Abstract
Diabetes mellitus and Parkinson’s Disease (PD) are debilitating diseases that are increasing in prevalence worldwide. One potential cause of these diseases is the accumulation of advanced glycation end products (AGEs), which are macromolecules that cause irreversible damages. AGEs are a diverse group of highly oxidative byproducts produced from α-dicarbonyl compounds (α-dcs), which are highly reactive molecules that bind indiscriminately to protein and DNA and, are regulated by a conserved glyoxalase system (GLO1 and DJ-1) in humans. Utilizing the conserved glyoxalase system, we were able to establish within a C. elegans model that when this glyoxalase system is impaired, the damages of α-dcs are reminiscent of diabetic complications. A recent review article identified novel single nucleotide polymorphisms (SNPs) associated with diabetic complications in humans. We performed an unbiased screen for the human SNPs utilizing RNA interference (RNAi) of the C. elegans orthologs, and discovered that RNAi of Gene X ameliorated α-dc pathologies such as neuropathy and stress. To understand the role this gene plays in regulating these pathologies, we examined its function both mechanistically and phenotypically. The finding of this work could allow for mechanistic control in the alleviation of debilitating diseases in humans such as diabetes and PD.