24th International Conference on Phosphorus Chemistry (ICPC24)

118 / 2023-10-10 08:58:22

The Site-specific Phosphorylated α-synuclein Fibrils Provide Structural and Mechanical Insights for Parkinson’s Disease

α-synuclein,Parkinson’s disease,structure,mechanism

Phosphorus Chemistry and Life & Health science > 1) Phosphorus chemistry in chemical biology

α-synuclein (α-syn) is predominantly associated with neurodegenerative disorders, including Parkinson's disease (PD). Phosphorylation at specific sites represents a critical post-translational modification (PTM) implicated in PD. In this study, we focused on the semi-synthesis of key phosphorylation sites, such as Tyr39 and Ser129, whose phosphorylation status has been linked to α-syn aggregation and the emergence of pathological features in PD. Our investigation revealed that phosphorylated α-syn fibrils exhibit distinct structural characteristics and demonstrate unique properties in terms of cellular uptake and propagation when compared to non-phosphorylated α-syn fibrils. Our findings underscore the significance of PTMs in influencing the polymorphism and membrane receptor binding affinity of α-syn fibrils.