Loss of function of Gene X protects against α-dicarbonyl stress through the skn-1 pathway in C. elegans

<p>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 (<em>GLO1</em> and <em>DJ-1</em>) in humans. Utilizing the conserved glyoxalase system, we were able to establish within a <em>C. elegans </em>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 <em>C. elegans </em>orthologs, and discovered that RNAi of <em>Gene X </em>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.</p>

Name thesis:degree_name

Master of Science

Level thesis:degree_level

Master's Thesis

Discipline thesis:degree_discipline

Biological Sciences

Year dc:date.available

2018

Author dc:creator

• Lim, Austin

Contributors dc:contributor

• Pankah Kapahi, PhD
• Wolfgang Schweigkofler, PhD

• alpha-dicarbonyl
• C. elegans
• diabetic complications
• neurodegenerative disease
• skn-1/NRF2 transcription factor
• Genetics
• Molecular Biology
• Molecular Genetics

Repository record dc:identifier

https://scholar.dominican.edu/masters-theses/351

OAI identifier oai:identifier

oai:scholar.dominican.edu:masters-theses-1363