Investigating Toxicant Induced Intracellular Zinc Modulation and Resultant TDP-43 Dysfunction Linked to Amyotrophic Lateral Sclerosis
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- August 20, 2022
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Arooji, Omeed
- Affiliation: College of Arts and Sciences
- Other Affiliation: Department of Neruology
- Abstract
- The majority of Amyotrophic Lateral Sclerosis (ALS) cases are sporadic, meaning they originate from unknown causes. This study proposes that mouse cortical neuron exposure to an environmental toxicant, here labeled TS5, induces intracellular modulation of zinc and produces dysfunctional, insoluble aggregates of TDP-43, a protein implicated in ALS pathology. Exposure of cortical neurons to TS5 alone resulted in the depletion of TDP-43 from the soluble fraction and visible bands in the insoluble fraction. Additionally, exposure to both ZnCl and TS5 resulted in higher intensity bands in the insoluble fraction and total depletion of TDP-43 from the soluble fraction. Moreover, the fluorescent dye NewPort Green was used to stain cortical neurons for cytoplasmic zinc ions. Images taken after exposure to TS5, TS5 and zinc, and zinc alone suggest that TS5 may modulate the intake of zinc into the cytoplasm by increasing its uptake. The introduction of bivalent metal chelators to exposed cortical neurons resulted in the rescue of pathological TDP-43 into the soluble fraction, serving as potential therapeutic avenues.
- Date of publication
- August 19, 2022
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