The Effects Of Oxidative Stress On P75ntr Signaling In Dopaminergic Neurons

<p>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. </p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Master's

Discipline thesis:degree_discipline

Biological Sciences

Grantor dc:publisher

Eastern Kentucky University

Year

2018

Author dc:creator

• Escobedo, Cassandra Marie

• Apoptosis
• LUHMES
• Neurotrophins
• Oxidative Stress
• p75
• p75 cleavage
• Molecular Biology

Statement dc:rights

• Copyright 2018 Cassandra Marie Escobedo

Repository record dc:identifier

https://encompass.eku.edu/etd/565

OAI identifier oai:identifier

oai:encompass.eku.edu:etd-1563