Characterization of novel neuroprotective ligands modulating molecular behavior of alpha synuclein in Parkinson's disease

• Main Author: Toh, Hui Ting
• Other Authors: Yoon Ho Sup
• Format: Theses and Dissertations
• Language: English
• Published: 2014
• Subjects: DRNTU::Science::Biological sciences::Biochemistry; DRNTU::Science::Biological sciences::Molecular biology
• Online Access: http://hdl.handle.net/10356/61684
• Institution: Nanyang Technological University

Parkinson’s Disease (PD) is a dreadful neurodegenerative condition which consumes most of the dopaminergic neurons in the substantia nigra region of the brain causing motor and non-motor distress in affected patients. Aggregated alpha synuclein (α-syn) is the main component in cytoplasmic inclusions called Lewy bodies in surviving neurons causing widespread cellular damage. Our laboratory designed a library of novel neuroprotective ligands which have yet been characterized and is the purpose of this study. Three potential ligands were selected based on preliminary cell-based drug screening and they were shown to interact with α-syn of which a potential ligand, D38, could increase the lag-time of α-syn fibrillation in vitro. They were further tested using synucleinopathy cell-based assays in PC12 cells which exhibited their neuroprotective potential and they were also able to reduce the expression of α-syn as well. As such, these novel ligands proved to have potential neuroprotective and anti-amyloid properties for treating PD.