Examining How Environmental Chemicals Affect Cellular Pathways Leading to Amyotrophic Lateral Sclerosis

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  • August 29, 2022
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  • Bhat, Vanya
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  • Amyotrophic Lateral Sclerosis (ALS) is a progressing motor neuron disease that affects neurons responsible for voluntary muscle movements such as walking, talking, and breathing. While therapies are developed to treat ALS symptoms, there is no cure for the disease. Toxic environmental chemicals such as pesticides have been found to increase the likelihood of ALS by causing the toxic aggregation of TDP-43, the hallmark protein of the disease. TDP-43 is typically found in the nucleus of neurons. However, in ALS, it delocalizes to the cytoplasm and forms toxic aggregates. Oxidative stress is another factor known to induce TDP-43 aggregation. This study examines whether two pesticides, TS1 and TS3, cause toxic TDP aggregation. Oxidative stress is also studied to see whether it is involved in response to pesticides. Results of this study show that TS1 and TS3 induce toxic TDP-43 aggregation. It is also observed that oxidative stress may play a role in toxic TDP-43 aggregation formation. Further examination of these pesticides and the effects of oxidative stress can lead to novel druggable targets for ALS therapy.
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