Are oligomers as toxic as we think ?
Parkinson`s disease (PD) is one of the most common neurodegenerative diseases. Dopaminergic neurons in substantia nigra and noradrenergic neurons in locus coeruleus develop characteristic filamentous inclusions in Parkinson’s disease known as Lewy bodies and neuritis.
Progression of PD is associated with cell death of DA neurons by permeabilization of oligomeric αS. Monomeric alpha-synuclein may interfere with the protofibril-specific permeabilization process.
You will deal with amyloid pore hypothesis which suggests that α-synuclein (αS) oligomers permeabilize cellular membranes and interfere with Ca homeostasis and cellular pathways. As a model system for membrane-αS oligomer interactions you will use giant unilamellar vesicles (GUVs). Binding of oligomeric and monomeric αS to GUVs will be monitored using confocal microscopy. You will study oligomer and monomer membrane permeabilization and binding using a dye release assay.
Your assignment will be:
Confocal images of DOPE-Rhod labeled GUVs and αS wt-140C-fluorescein monomers-binding experiments (scale bar corresponds to 10 µm). Lipids (left) and monomers (right).
If you are interested in this Master assigment, you can contact:
Anja Stefanović, MSc in medical biochemistry,
MESA+ Institute for Nanotechnology
Faculty of Science and Technology
Zuidhorst ZH 167
7522 NB Enschede
phone: +31 53 489 4612
phone 2: +31 53 489 3157