Study the Effect of Chinese Medicinal Compounds on the Aggregation of Alpha Synuclein: Potential Therapeutic Implications in Parkinson's Disease

Alpha-synuclein (α-syn) is a neuronal protein that plays a major role in the pathogenesis of a cluster of neurodegenerative diseases known as synucleinopathies, amongst which is Parkinson's disease (PD). These diseases are characterized by the abnormal intracellular aggregation of α-syn, which is known to be a key pathogenic event of these diseases. Therefore, identifying compounds that inhibit the aggregation of α-syn might have potential therapeutic implications. It is known that the Chinese Medicinal Compounds were used as a remedies for many neurodegenerative diseases such PD. In this thesis, we aim to test the effect of four of these compounds (salvianolic acid B (Sal B), dihydromyricetin, Geniposide, and bilobalide) on the aggregation process of α-syn using in vitro biochemical and cell culture techniques. To achieve this goal, we produced recombinant α-syn and purified it using size exclusion chromatography. The protein was extensively characterized using different approaches (SDS-PAGE, Immunoblotting, Mass Spec, and Thioflavin-S aggregation assays). Our results showed that the recombinant protein displays the well-known characteristic features of α-syn protein and exhibit a pronounced ability to aggregate and form fibrils in vitro. Similarly, intracellular aggregation of α-syn was observed in a neuronal cell model after treatment with exogenous fibrils (seeds). Interestingly, of the compounds tested, Sal B was the only one to interfere with α-syn aggregation in vitro and in cell culture. These results are promising to further investigate the possibility of using Sal B as an inhibitor of α-syn aggregation process and in turn as a putative compound to treat PD and other synucleinopathies.