Author ORCID Identifier
Document Type
Dissertation
Date of Award
2022
Degree Name
Doctor of Philosophy (PhD)
Department
Basic Biomedical Science
First Advisor
Samuel S Newton
Abstract
Erythropoietin (EPO) is a cytokine hormone known for initiating red blood cell proliferation by binding to its homodimer receptor (EPOR)2 in the bone marrow. Recent progress in neurobiology has shown that EPO also exerts robust neurotrophic and neuroprotective activity in the CNS. It is widely thought that EPO’s neurotrophic activity is centrally involved in its antidepressant and cognitive enhancing effects. However, EPO’s potent erythropoietic effects prevent it from being used in the clinic to treat psychiatric disorders. A chemically engineered non-erythropoietic derivative of EPO, carbamoylated EPO (CEPO), produces psychoactive effects without activating hematopoiesis. However, CEPO is expensive to produce and batch variability limits its potential as pharmacotherapy. Using CEPO as a template, our lab has expressed and characterized two triple substitution mutants of EPO (known as QPO and RPO) in-vitro, in-vivo, and in-silico to determine their neurotrophic activity, behavioral effects, and ligand-receptor interactions.
Subject Categories
Biochemistry | Computational Chemistry | Computational Neuroscience
Keywords
Antidepressant, Carbamoylated erythropoietin, mimetic, molecular dynamics, neurotrophic, Nonhematopoietic
Number of Pages
64
Publisher
University of South Dakota
Recommended Citation
Pekas, Nicholas John, "NONHEMATOPOIETIC ERYTHROPOIETIN: A STUDY OF SIGNALING, STRUCTURE, AND BEHAVIOR" (2022). Dissertations and Theses. 31.
https://red.library.usd.edu/diss-thesis/31
Included in
Biochemistry Commons, Computational Chemistry Commons, Computational Neuroscience Commons