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.
","abstract_html":"<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>","abstract_has_math":false,"creators":["Escobedo, Cassandra Marie"],"institution":"Eastern Kentucky University","degree_name":"Master of Science (MS)","degree_level":"Master's","degree_discipline":"Biological Sciences","degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-01-01T08:00:00Z","date_published":"2018-01-01T08:00:00Z","updated_at":"2026-07-24T02:15:47Z","subjects":["Apoptosis","LUHMES","Neurotrophins","Oxidative Stress","p75","p75 cleavage","Molecular Biology"],"languages":[],"rights":["Copyright 2018 Cassandra Marie Escobedo"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://encompass.eku.edu/etd/565","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Escobedo, Cassandra Marie"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:publisher","label":"Institution","values":["Encompass Digital Archive, Eastern Kentucky University"]},{"key":"dc:type","label":"Dc Type","values":["Master Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biological Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Master's"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (MS)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Eastern Kentucky University"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Apoptosis","LUHMES","Neurotrophins","Oxidative Stress","p75","p75 cleavage","Molecular Biology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2018 Cassandra Marie Escobedo"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://encompass.eku.edu/etd/565"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:format","label":"Dc Format","values":["application/PDF"]},{"key":"dc:source","label":"Dc Source","values":["Encompass Digital Archive: Online Theses and Dissertations"]},{"key":"dc:title","label":"Title","values":["The Effects Of Oxidative Stress On P75ntr Signaling In Dopaminergic Neurons"]}]}],"canonical_facts":{"dc:creator":["Escobedo, Cassandra Marie"],"dc:description.abstract":["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.
"],"dc:format":["application/PDF"],"dc:identifier":["https://encompass.eku.edu/etd/565"],"dc:publisher":["Encompass Digital Archive, Eastern Kentucky University"],"dc:rights":["Copyright 2018 Cassandra Marie Escobedo"],"dc:source":["Encompass Digital Archive: Online Theses and Dissertations"],"dc:subject":["Apoptosis","LUHMES","Neurotrophins","Oxidative Stress","p75","p75 cleavage","Molecular Biology"],"dc:title":["The Effects Of Oxidative Stress On P75ntr Signaling In Dopaminergic Neurons"],"dc:type":["Master Thesis"],"thesis:degree_discipline":["Biological Sciences"],"thesis:degree_level":["Master's"],"thesis:degree_name":["Master of Science (MS)"],"thesis:institution_name":["Eastern Kentucky University"]},"updated_at":"2026-07-24T02:15:47Z"}