Particulate Air Pollutants Exacerbate Polyglutamine Aggregation in C. elegans
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Authors
Dagnachew, Mesgana
Green, Emily
Kikis, Elise
Issue Date
2020
Type
Presentation
Language
en_US
Keywords
Scholarship Sewanee 2020 , Proteostasis network , Nano-particulate matter , Air pollution , C. elegans , Proteostasis , Neurodegenerative diseases , Polyglutamine diseases , Protein misfolding , Protein aggregation
Alternative Title
Abstract
The proteostasis network refers to the biochemical pathways that together regulate protein synthesis, transport, folding, and degradation. Functional decline in the proteostasis network activity results in protein misfolding, aggregation, and, often, toxicity. Diseases of protein conformation, such as Alzheimer’s disease (AD), Huntington’s disease (HD), and Machado-Joseph disease (MJD) seem to have proteostasis collapse at their core. Interestingly, recent studies showed that particulate air pollution may be a significant environmental risk factor for AD. Some studies have suggested that poor air quality, specifically nanoparticulate matter (nPM), provokes the aggregation and toxicity of neurodegenerative disease-associated proteins resulting in cognitive decline in mouse models of AD. We propose that nPM may act through the proteostasis network to indirectly disrupt the folding of disease-associated proteins. We are currently testing the hypothesis that the proteostasis machinery and the folding of neurodegenerative disease-associated proteins, such as huntingtin (htt), and polyQ expansions, expressed in C. elegans can be affected by controlled extrinsic factors. To induce proteostasis disruption, we treated wild type animals with sodium azide (Na-Azide), azetidine (AZC), paraquat (PQ), and heat shock, which are all known to disturb protein folding, and determined sub-lethal concentrations for each chemical. In preliminary studies of the effect of these proteostasis-disrupting agents on htt protein folding, we exposed C. elegans that have been engineered to express a fragment of the human htt protein in body wall muscle cells. Exposure of animals expressing human htt in body wall muscle cells to 5mM AZC or 5mM Na-Azide resulted in a statistically significant increase in protein aggregation. To investigate the effect of nPM on protein aggregation in C. elegans, we exposed polyQ-expressing animals to nPM and measured aggregation. Animals exposed to nPM displayed a statistically significant increase in polyQ aggregation in comparison to unexposed animals. Overall, our study suggests that nano-sized particulate air pollution exacerbates the misfolding of neurodegenerative disease-associated proteins in C. elegans. Thus, we propose that proteostasis disruption in response to nPM may be a significant determinant in the onset of neurodegenerative disease.
Description
Citation
Publisher
University of the South