Nanoparticulate air pollution disrupts proteostasis in Caenorhabditis elegans

作者：Bailey A. Garcia Manriquez, Julia A. Papapanagiotou, Claire A. Strysick, Emily H. Green, Elise A. Kikis · 发表于：PLoS ONE · 年份：2023 · DOI：10.1371/journal.pone.0275137 · 被引用次数：9 · 研究领域：Fibromyalgia and Chronic Fatigue Syndrome Research、Genetics, Aging, and Longevity in Model Organisms、Spaceflight effects on biology

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 mo...