Environmental stressors contribute to Alzheimer’s disease-related protein misfolding

Thumbnail Image
Garcia Manriquez, Bailey
Papapanagiotou, Julia A.
Strysick, Claire A.
Rajasekaran, Prisha
Studivant, Jeremiah J.
Green, Emily H.
Kikis, Elise A.
Issue Date
Scholarship Sewanee 2022 , proteostasis , protein misfolding , Alzheimer's Disease , air pollution , environmental stressors
Air pollution has been previously identified as a known risk factor for Alzheimer’s Disease (AD) development. As a progressive neurodegenerative disease, AD is associated with symptoms such as memory loss, cognitive deterioration, dementia, and difficulty completing daily activities. The causes of AD development are complicated and partially unknown, but are thought to be associated with protein aggregation and overarching proteostasis collapse. The proteostasis network works to control and maintain protein synthesis, restoration, and degradation in the cell. Amyloid beta (Aβ) and tau are proteins shown to misfold and aggregate during AD progression, and exposure to the environmental stressor nano-particulate matter (nPM) derived from air pollution has been shown to increase Aβ aggregation in mouse models. We asked whether there is a specific link between nPM exposure and proteostasis collapse. To determine whether this is true, we utilized the model organism Caenorhabditis elegans expressing disease-associated proteins polyQ and Abeta as sensors of proteostasis decline in a variety of tissues. We found that animals expressing polyQ35 and polyQ40 in the body wall muscle cells and polyQ44 in their intestinal lining cells exhibit increased aggregation. Decreased mobility upon exposure to nPM was also shown when compared to controls. Animals expressing Aβ in body wall muscle cells showed increased formation of large, visible, protein aggregates and associated toxicity upon exposure to nPM when compared to controls. To determine whether these findings reflect changes in proteostasis network gene expression, wildtype N2 animals were exposed to nPM and showed increased gene expression of the oxidative stress responsive gst-4 and dysregulated gene expression of the molecular chaperones hsp-4, C12C8.1, and F44E5.4. Overall, our data suggests that exposure to air pollution exacerbates AD via protein misfolding.