Nanoparticulate air pollution disrupts proteostasis in Caenorhabditis elegans

• Published in: PloS one Vol. 18; no. 2; p. e0275137
• Main Authors: Garcia Manriquez, Bailey A, Papapanagiotou, Julia A, Strysick, Claire A, Green, Emily H, Kikis, Elise A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23-02-2023; Public Library of Science (PLoS)
• Subjects: Age; Agglomeration; Aging; Air pollution; Air Pollution - adverse effects; Alzheimer Disease; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animals; Biology and Life Sciences; Body wall; Caenorhabditis elegans; Caenorhabditis elegans - metabolism; Data points; Dementia disorders; Ecology and Environmental Sciences; Environmental risk; Fluorescence; Folding; Health risk assessment; Health risks; Huntington's disease; Huntingtons disease; Hypotheses; Influence; Medicine and Health Sciences; Molecular weight; Muscles; Nanoparticles; Nematodes; Neurodegenerative diseases; Neurodegenerative Diseases - metabolism; Neurotoxicity; Oligomerization; Paralysis; Phenotypes; Physiological aspects; Protein biosynthesis; Protein folding; Protein interaction; Protein synthesis; Protein transport; Proteins; Proteomes; Proteostasis; Proteostasis Deficiencies; Research and Analysis Methods; Risk factors; Signs and symptoms; United States; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0275137

The proteostasis network comprises the biochemical pathways that together maintain and regulate proper protein synthesis, transport, folding, and degradation. Many progressive neurodegenerative diseases, such as Huntington's disease (HD) and Alzheimer's disease (AD), are characterized by an age-dependent failure of the proteostasis network to sustain the health of the proteome, resulting in protein misfolding, aggregation, and, often, neurotoxicity. Although important advances have been made in recent years to identify genetic risk factors for neurodegenerative diseases, we still know relatively little about environmental risk factors such as air pollution. Exposure to nano-sized particulate air pollution, referred to herein as nanoparticulate matter (nPM), has been shown to trigger the accumulation of misfolded and oligomerized amyloid beta (Aβ) in mice. Likewise, air pollution is known to exacerbate symptoms of AD in people. We asked whether nPM contributes to the misfolded protein load, thereby overwhelming the proteostasis network and triggering proteostasis decline. To address this, we utilized C. elegans that express reporter proteins that are sensitive to changes in the protein folding environment and respond by misfolding and displaying readily scorable phenotypes, such as localized YFP fluorescence or paralysis. We found that nPM exacerbated protein aggregation in body wall muscle cells, increasing the number of large visible protein aggregates, the amount of high molecular weight protein species, and proteotoxicity. Taken together, the data point to nPM negatively impacting proteostasis. Therefore, it seems plausible that nPM exposure may exacerbate symptoms of AD and age-related dementia in a manner that is at least partially dependent on proteostasis decline.