Figure 7
From: Low doses of bioherbicide favour prion aggregation and propagation in vivo
Schema illustrating the dual effect of A6 biopesticide on prion aggregation and propagation. (a) A6-mediated stabilization of soluble prion oligomers at low doses. Incubation of prion-infected brain homogenate with a low dose (0.25 mM) of A6 in vitro, allows formation of soluble rSDS-PrPSc oligomers (50–75 kDa) (1) that remains in the supernatant (S), whereas insoluble rSDS-PrPSc oligomers concentrated in the pellet fraction (P) are not formed (2). In vivo treatment of mice with a low dose of A6 (5 mg/kg) decreases animals’ survival time and increases prion amyloid deposits suggesting that soluble rSDS-PrPSc oligomers are toxic. These species are not visible in 5 mg/kg A6-treated mice brains. (b) A6-mediated stimulation of prion aggregation at high doses. Incubation of prion-infected brain homogenate with the highest dose (1.5 mM) of A6 in vitro, allows formation of insoluble rSDS-PrPSc oligomers (50–75 kDa) (2) mainly in the pellet fraction (P). In vivo treatment of mice with higher doses of A6 (10 and 20 mg/kg) increases animals’ survival time and decreases prion amyloid deposits suggesting that insoluble rSDS-PrPSc oligomers are less toxic. These species are quite abundant in mice brains treated with 20 mg/kg of A6, suggesting that insoluble rSDS-PrPSc oligomers have a rather protective role.
