This dissertation details my Ph.D. work in Dr. Sreeganga Chandra's laboratory at Yale University studying regulators of α-synuclein aggregation in Parkinson's disease. I first discuss my work probing the molecular mechanism behind GBA-linked Parkinson's disease. Using in vitro methods, mouse lines, and iPSC-derived human neurons, I show that glycosphingolipids accumulating as a result of GBA mutations promote a-synuclein aggregation, leading to an increased risk for Parkinson's disease in affected populations. I then describe my work studying the effects of a chaperone disaggregase complex on mitigating a-synuclein aggregation. Through the characterization of an established Parkinson's disease mouse line crossed with a line overexpressing the disaggregase machinery, I show that the chaperone disaggregase complex is capable of mitigating asynuclein pathology in vivo.
Together, my thesis work describes two cellular players involved in both promoting and preventing pathological α-synuclein aggregation in Parkinson's disease, contributing to our knowledge of the disease and informing on potential therapeutic targets in treating Parkinson's disease.
|School Location:||United States -- Connecticut|
|Source:||DAI-B 79/12(E), Dissertation Abstracts International|
|Subjects:||Molecular biology, Neurosciences|
|Keywords:||Alpha-Synuclein, Chaperone, GBA, Parkinson's Disease|
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