Figure 12.

Biological consequences of blocking α-syn CT truncation by passive immunotherapy. A, Schematic representation of a neuron overexpressing α-syn in the α-syn tg mouse model. α-syn oligomers are released to the extracellular environment, together with calpain-1. Extracellular α-syn oligomers can propagate to other neurons and glial cells. Furthermore, α-syn oligomers can also be cleaved by calpain-1, generating extracellular CT-α-syn, which is more prone to aggregation and subsequent neurotoxicity. B, In tg animals immunized with CT α-syn antibodies, propagation of extracellular α-syn oligomers is inhibited and α-syn is protected from CT truncation. The rate of α-syn aggregation is thus diminished and α-syn oligomers can be effectively directed toward clearance pathways.