Show simple item record

dc.contributor.authorDagnachew, Mesgana
dc.contributor.authorGreen, Emily
dc.contributor.authorKikis, Elise
dc.date.accessioned2020-04-23T02:40:30Z
dc.date.available2020-04-23T02:40:30Z
dc.date.issued2020
dc.identifier.urihttps://dspace.sewanee.edu/handle/11005/21701
dc.description.abstractThe 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.en_US
dc.description.sponsorshipAppalachian College Association Faculty Fellowship to Professor Kikis Faculty Development Grant, The University of the South, to Professor Kikisen_US
dc.language.isoen_USen_US
dc.publisherUniversity of the Southen_US
dc.subjectScholarship Sewanee 2020en_US
dc.subjectProteostasis networken_US
dc.subjectNano-particulate matteren_US
dc.subjectAir pollutionen_US
dc.subjectC. elegansen_US
dc.subjectProteostasisen_US
dc.subjectNeurodegenerative diseasesen_US
dc.subjectPolyglutamine diseasesen_US
dc.subjectProtein misfoldingen_US
dc.subjectProtein aggregationen_US
dc.titleParticulate Air Pollutants Exacerbate Polyglutamine Aggregation in C. elegansen_US
dc.typePresentationen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record