Dr. Blagovesta Popova

Molecular basis of Parkinson’s disease: Yeast as model system
 

Parkinson’s disease is the second most common neurodegenerative disorder. Proteinaceous aggregates are formed and deposited in specific regions of the brain. A major player is the protein α-synuclein which forms fibrils and aggregates that lead to dysfunction and death of neurons.

We use yeast (Saccharomyces cerevisiae) to model disease states, since many key cellular pathways such as membrane trafficking, protein aggregation and regulated protein turnover are conserved between human and yeast. Expression of α-synuclein in yeast cells results in its localization to the plasma membrane, growth impairment and formation of intracellular aggregates, similar to neurons of Parkinson patients. We examine the correlation between α-synuclein cytotoxicity, protein aggregation and localization pattern, as well as the role of α-synuclein post-translational modifications. By means of high-throughput screen of yeast essential mutant strains we are looking for modulators of α-synuclein induced toxicity.

α-synuclein in yeast

• Protein modifications: SUMOylation and phosphorylation and their role for α-synuclein related cytotoxicity


• Chemical Stress: Effect of nitrative and oxidative stress on α-synuclein aggregation and toxicity


• Essential genes: genome-wide screen for modifiers of α-synuclein toxicity