(31) The Impact of Poor Air Quality on Proteostasis and Neurodegenerative Disease

The proteostasis network refers to the pathways that regulate protein synthesis, transport, folding, and degradation. Functional decline in the activity of this network results in protein misfolding, aggregation, and toxicity,... [ view full abstract ]

The proteostasis network refers to the pathways that regulate protein synthesis, transport, folding, and degradation. Functional decline in the activity of this network results in protein misfolding, aggregation, and toxicity, which is observed in patients with progressive neurodegenerative disorders such as Alzheimer’s disease (AD), Huntington’s disease (HD) and Machado Joseph disease. Age-related decline in proteostasis is thought to be a vital contributor to the aforementioned diseases. 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 small particulate air matter (PM2.5), provokes the aggregation and toxicity of neurodegenerative disease-associated proteins resulting in cognitive function decline in mouse models of AD. We propose that PM2.5 indirectly disrupts the folding of disease-associated proteins through the proteostasis network. To test this, we will feed PM2.5 to a C. elegans model with temperature-sensitive alleles. Temperature sensitive proteins have served as sensors of protein misfolding in vivo and will allow us to examine whether PM2.5 triggers a disruption of proteostasis. We have characterized the phenotypes of the temperature sensitive C. elegans at the restrictive temperature, 25℃, and the permissive temperature, 15℃. We found that those exposed to 25℃ exhibited greater difficulties with movement and/or development. We are currently testing the hypothesis that the proteostasis machinery can be affected by environmental factors. Our controls include known protein-damaging agents including sodium azide (Na-Azide), azetidine (AZC), and heat shock. We observed delayed movement in the worms treated with Na-Azide and AZC. We will elucidate the mechanism by which they function and determine whether PM2.5 functions similarly. Overall, our study should lead to a greater understanding of the mechanism(s) by which poor air quality exacerbates neurodegenerative diseases, which should aid in the development of therapeutic intervention and prevention approaches.