Honors Theses
Date of Award
Spring 4-30-2021
Document Type
Undergraduate Thesis
Department
Chemistry and Biochemistry
First Advisor
Jason Paris
Second Advisor
Nicole Ashpole
Third Advisor
Saumen Chakraborty
Relational Format
Dissertation/Thesis
Abstract
Great advances have been made in the treatment of HIV, however, new infections remain consistent each year with no effective cure. The early entry of HIV virus into the central nervous system is thought to contribute to the development of HIV-associated neurocognitive disorders. One of the mechanisms of neurological impairment may involve actions of the neurotoxic HIV viral protein, trans-activator of transcription (Tat). Tat can be secreted from infected cells and acts as an excitotoxin, increasing the intracellular flux of Ca2+ , promoting mitochondrial dysfunction, and neural cell damage/death. Previous experiments have shown that steroid hormones such as estrogen can exert protective effects against Tat-mediated neurotoxicity; but, the site(s) of this protection action are unclear. The primary purpose of this thesis was to begin to assess the role of the non-traditional estrogen receptor, G-protein coupled receptor 1 (GPER1), in Tat-mediated neurotoxicity. The capacity of a GPER1 agonist and antagonist were assessed for their influence on Tat-induced production of reactive oxygen species (ROS) and subsequent cell death using SH-SY5Y human neuroblastoma cells. The results revealed that GPER1 agonism attenuated Tat induced ROS production and prevented Tat-mediated cell death. Conversely, antagonizing GPER1 modestly reduced ROS production; albeit, did not completely attenuate Tat-mediated increases, and exert no effects on cell death. Further investigation of non-traditional sites of endocrine action may reveal novel therapeutic targets for the treatment of neurological diseases, within and beyond the field of neuroHIV.
Recommended Citation
Thapa, Shiwani, "Potential Interactions Between GPER1 and HIV Tat-mediated Neurotoxicity" (2021). Honors Theses. 1891.
https://egrove.olemiss.edu/hon_thesis/1891
Accessibility Status
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