Investigating The Role Of LC3B In The Seeding Of Alpha-synuclein In Parkinson’s Disease Model Systems

Porte-Trachsel, Natalie
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University of Guelph

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease. Despite this prevalence, and the significant impact PD has on the quality of life of patients, there are no effective treatments to halt progression. As more evidence emerges regarding the behaviour of α-syn as a prion-like protein, more research is needed to investigate the mechanism behind how α-syn seeds cell-to-cell. Here, I show that SNCA mutant neurons transmit PD pathology (PS129) to nod-scid gamma mice via cell engraftment. I also show that exosomes isolated from SNCA mutant neurons can facilitate the seeding of PD pathology (aggregated α-syn) to primary neurons, decreasing neurite length, maturity, and firing. Finally, I confirm that C-terminus and N-terminus truncations of α-syn disrupt the interaction with LC3B, thereby reducing the rate of seeding of aggregated and total α-syn via these exosomes. Overall, these findings suggest a potential mechanism for the seeding of α-syn between cells.

Molecular Biology, Cellular Biology, Stem cell, Autophagy, Parkinson's Disease, Exosomes