MGluR5 Modulation Effect on Protein Degradation in Parkinson's Disease

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Creator: 

Xing, Viktoria

Date: 

2020

Abstract: 

Parkinson's disease (PD) is the second most common neurodegenerative disease that is characterized by motor symptoms and dysregulation of the dopaminergic system. One of the main hallmarks of PD is abnormal alpha-synuclein (a-syn) aggregation. In our experiment a-syn fibrils and A53T adenovirus will be added to SH-SY5Y cells to mimic PD conditions of protein aggregation and overexpression. This thesis investigates the possibility of clearing a-syn fibrils from SH-SY5Y cells using an allosteric mGluR5 inhibitor, CTEP. We found that CTEP contributed to significant elimination of a-syn fibrils form SH-SY5Y cells. Assessment of AKT/mTOR pathway has shown that CTEP action is mTOR dependent. Additionally, we found a significant upregulation of autophagy system components, such as Beclin1, Atg5-Atg12 complex, Atg7, Atg101 and Atg3, and significant downregulation of inhibitory pULK1 in response to CTEP administration. We conclude that CTEP is a useful pharmacological agent in managing abnormal a-syn aggregation.

Subject: 

Neuroscience

Language: 

English

Publisher: 

Carleton University

Thesis Degree Name: 

Master of Science: 
M.Sc.

Thesis Degree Level: 

Master's

Thesis Degree Discipline: 

Neuroscience

Parent Collection: 

Theses and Dissertations

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