Diesel Particulate Matter Induces Toxicity Within Caenorhabditis elegans in a Manner Distinct from Protein Misfolding
Authors
Studivant, Jeremiah
Issue Date
2024-05-01
Type
Thesis
Language
en_US
Keywords
University of the South , Biology Department , Sewanee Senior Honors Theses 2024 , Air pollution , C. elegans , proteostasis , Biology
Alternative Title
Abstract
Neurodegenerative diseases are characterized by the age-dependent failure of the
proteostasis network (PN)—a critical regulator of protein folding, trafficking, and
degradation—leading to an inability to maintain protein folding homeostasis (proteostasis) and eventually resulting in accelerated loss of neurons. Huntington’s disease (HD) is a
neurodegenerative disorder caused by a mutation within the huntingtin gene, encoding an
expansion of a glutamine (polyQ) repeat. This polyQ expansion is prone to misfolding,
perturbing proteostasis. While significant advances have been achieved in understanding risk factors for neurodegenerative diseases, the impact of air pollution on their progression represents a novel and emerging area of concern. Despite the global prevalence of pollutant exposure, our understanding of its effect on the progression of neurodegenerative diseases is limited. Previous work has demonstrated that nanoparticulate matter (nPM) exacerbates proteostasis failure, increasing polyQ protein toxicity in C. elegans. Yet, the variable composition of nPM, influenced by factors such as collection time and geographic location, can result in inconsistent bioactivity assessments for experimental reproduction. Therefore, we began focusing on the effect of a more refined particle, specifically, investigating the effect of commercially available diesel particulate matter (dPM) on proteostasis. To examine proteostasis integrity we employed a C. elegans model expressing a polyQ sequence, fused to a yellow fluorescent protein (YFP), as a sensor of the protein folding environment. Surprisingly, we found that dPM induces cellular toxicity in a manner that is independent of polyQ misfolding. Identifying the effect dPM has on proteostasis offers new insight into how nano pollutants may influence the progression of neurodegenerative diseases.
Description
Citation
Publisher
University of the South