Characterization of α-synuclein isoforms SUMOylation profile and its impact on α-synuclein homeostasis and pathophysiology in Parkinson’s disease



Research team: Marco Feligioni, Kambiz Hassanzadeh

To date, four splice isoforms have been identified for α-synuclein (AS), the major component of the abnormal protein aggregation in Lewy bodies of Parkinson’s disease (PD). In comparison to wild type α-synuclein (AS-140), little is known about its splice isoforms and how they affect neuronal functions. Post-translational modifications such as ubiquitination and small ubiquitin- like modification (SUMOylation) of α-synuclein regulate several of its properties, including aggregation and degradation. Considering the limited information on α-synuclein isoforms and importance of SUMOylation in regulating of proteins function, this study has been aimed to characterize the SUMOylation of α-Synuclein isoforms profile and its impact on α-Synuclein homeostasis and pathophysiology of Parkinson’s disease.

In order to cover the aims, three experimental approaches and methods have been designed including the cell part, neuronal assessments and human blood and brain experiments. First we will evaluate the effect of rotenone on α-Synuclein isoforms profile expression and α- Synuclein aggregation in neuroblastoma cell line (SH-SY5Y). As the second aim we will check the mutual effect of SUMOylation and α-Synuclein isoforms profile expression on α-Synuclein aggregation in cell line as well as human blood samples and post mortem brain tissue. And finally the impact of α-Synuclein isoforms diversity and their SUMOylation on synaptic function will be evaluated in neurons. It is noteworthy that this proposal is a part of our larger interests on studying SUMOylation molecular targets in neurodegenerative diseases. The role of SUMO on α-Synuclein isoforms is a novel cutting-edge research interest on PD we will include in our future planning.