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Full text release has been delayed at the author's request until January 01, 2027

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Mechanisms of Cell-to-Cell Propagation of α-Synuclein in Parkinson's Disease

Baitamouni, Sarah
http://orcid.org/0000-0003-4476-3272
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou163726792998047

Abstract Details

2021, Master of Science (MS), Ohio University, Biological Sciences (Arts and Sciences).
Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder characterized by the loss of dopaminergic (DA) neurons in substantia nigra pars compacta and the formation of Lewy Bodies (LBs), cytoplasmic protein deposits of α-Synuclein (αSyn). In recent years, an intriguing concept of prion-like spreading of pathogenic proteins such as αSyn has emerged. Released αSyn spreads between neurons causing neurodegeneration, but the actual propagation mechanism is still under investigation. In order to test cell-to-cell propagation of αSyn, I investigate αSyn release. In my project, I develop a larval neuromuscular junction (NMJ) model in order to study αSyn release mechanisms. I hypothesize that neuronal activity regulates pathological αSyn release. Thus, using optogenetics to stimulate neurons that co-express αSyn and Channel Rhodopsin (ChR2) in Drosophila melanogaster larvae, I examine αSyn release induced by neuronal depolarization. I use ELISA technique to detect and compare released αSyn levels in the hemolymph of different fly lines. Results show activity-dependent αSyn release. This activity-dependent αSyn release is also influenced by synaptic transmission, mutations, and phosphorylation of αSyn. Hence, αSyn release might be induced in some regions of PD brain in response to excitability, and this αSyn release might underlie the disease progression. Therefore, targeting αSyn release could be further studied in hope of establishing new therapeutic interventions to stop or slow PD pathology.
Daewoo Lee (Advisor)
Corinne Nielsen (Committee Member)
Robert Colvin (Committee Member)
97 p.
Biology; Neurobiology; Neurosciences
Parkinson’s disease; neurodegenerative disease; neurodegeneration; movement disorder; dopaminergic neurons; substantia nigra pars compacta; lewy bodies; α-synuclein (αSyn); α-synuclein release; α-synuclein cell-to-cell propagation; α-synuclein aggregation; Drosophila animal model; larval neuromuscular junction; glutamatergic neurons.

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Citations

  • Baitamouni, S. (2021). Mechanisms of Cell-to-Cell Propagation of α-Synuclein in Parkinson's Disease [Master's thesis, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou163726792998047

    APA Style (7th edition)

  • Baitamouni, Sarah. Mechanisms of Cell-to-Cell Propagation of α-Synuclein in Parkinson's Disease. 2021. Ohio University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou163726792998047.

    MLA Style (8th edition)

  • Baitamouni, Sarah. "Mechanisms of Cell-to-Cell Propagation of α-Synuclein in Parkinson's Disease." Master's thesis, Ohio University, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou163726792998047

    Chicago Manual of Style (17th edition)

ohiou163726792998047
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This open access ETD is published by Ohio University and OhioLINK.