Author ORCID Identifier

https://orcid.org/0000-0003-4091-3683

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

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