Date of Award

January 2018

Degree Type

Open Access Thesis

Document Type

Master Thesis

Degree Name

Master of Science (MS)


Biological Sciences

First Advisor

Bradley R. Kraemer

Department Affiliation

Biological Sciences

Second Advisor

Lindsay E. Calderon

Department Affiliation

Biological Sciences

Third Advisor

Tanea T. Reed

Department Affiliation



The p75 neurotrophin receptor (p75NTR) is responsible for implementing cellular death during embryonic development and in response to cellular injury. The receptor has been recognized as a contributor of neurodegeneration in numerous pathological conditions. Cleavage of p75NTR by Tumor Necrosis Factor converting enzyme (TACE) and γ-secretase has been observed to be associated with an increase in neurodegeneration. In a previous study, p75NTR was discovered to become activated in sympathetic neurons in response to oxidative stress induced by 4-hydroxynonenal (HNE) in a ligand-independent mechanism. Furthermore, cleavage of the receptor was demonstrated to contribute to the death of sympathetic neurons following oxidative insult. This study investigates the effects of oxidative stress on p75NTR signaling in dopaminergic neurons. Because dopaminergic neurons only compromise a very small percentage of the ventral midbrain, the Lund Human Mesencephalic cell line (LUHMES) was used in our study. LUHMES cells can be differentiated into mature dopaminergic neurons following a two-step differentiation procedure. The p75NTR was found to be activated and cleaved in response to 6-hydroxydopamine (6-OHDA), a neurotoxin frequently used to mimic oxidative stress in dopaminergic neurons. Furthermore, the pretreatment of dopaminergic neurons with a ligand-blocking antibody specific for the extracellular domain of p75NTR (α- p75 NTR ECD) failed to protect neurons from 6-OHDA-induced death. Our results suggest that p75NTR may contribute to the death of dopaminergic neurons exposed to oxidative stress in a ligand-independent manner.