Date of Award
2024
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Biological Sciences
Committee Chair
Jerome Baudry
Committee Member
Joseph Ng
Research Advisor
Bradley Kraemer
Subject(s)
Parkinson's disease--Treatment, Nervous system--Degeneration, Nerve tissue proteins, Neurotransmitter receptors
Abstract
The p75 Neurotrophin Receptor (p75NTR) is a multifunctional transmembrane protein expressed in distinct regions of the adult nervous system. p75NTR regulates various functions, including neuronal survival or apoptosis interacting with coreceptors Trk receptors or sortilin. Activation of p75NTR occurs through proteolytic processing, and we previously demonstrated that oxidative stress induces activation of p75NTR in LUHMES cells, a neuronal cell line derived from the human ventral mesencephalon. Dopaminergic neurons of the ventral mesencephalon are vulnerable to oxidative stress and neurodegeneration associated with Parkinson’s disease (PD). Thus, we evaluated the mechanisms behind p75NTR activation and its physiological implications in a PD model. Our findings reveal that oxidative stress induces proteolytic processing of p75NTR in LUHMES cells, promoting internalization into endosomes. We also found that pharmacological modulation of p75NTR using LM11A-31 protects LUHMES cells from neurite degeneration and reduces apoptosis associated with oxidative stress, indicating p75NTR as a potential therapeutic target for PD.
Recommended Citation
Pokharel, Poshan, "Small molecule modulation of the p75 Neurotrophin Receptor attenuates neurodegeneration in an in vitro model of Parkinson’s disease" (2024). Theses. 660.
https://louis.uah.edu/uah-theses/660