MGluR5 Modulation Effect on Protein Degradation in Parkinson's Disease
Public Deposited- Resource Type
- Creator
- 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
- Language
- Publisher
- Thesis Degree Level
- Thesis Degree Name
- Thesis Degree Discipline
- Identifier
- Rights Notes
Copyright © 2020 the author(s). Theses may be used for non-commercial research, educational, or related academic purposes only. Such uses include personal study, research, scholarship, and teaching. Theses may only be shared by linking to Carleton University Institutional Repository and no part may be used without proper attribution to the author. No part may be used for commercial purposes directly or indirectly via a for-profit platform; no adaptation or derivative works are permitted without consent from the copyright owner.
- Date Created
- 2020
Relations
- In Collection:
Items
Thumbnail | Title | Date Uploaded | Visibility | Actions |
---|---|---|---|---|
xing-mglur5modulationeffectonproteindegradation.pdf | 2023-05-05 | Public | Download |