Figure 4.
Disruption of Y10–S26 interaction impairs fibril formation. A, Model of interprotofibrillar Aβ42. The interaction between Y10 and S26 stabilizes the fibril and contributes to its progression. B, Upon the nitration of Y10, because the nitro group is negatively charged, it is arrested by the side-chains of either R5 or H6, impeding its interaction with S26 and destabilizing the fibril. C, Our mutant H14 to E14 also would trigger a rearrangement of the side-chains of the N terminus, disrupting the interaction between Y10 and S26 as it happens upon nitration. D, ThT fluorescence after 72 h of aggregation of Aβ42, Aβ42 treated with 100 μm SIN-1, synthetically nitrated Aβ42 (AβNTyr), and AβE14 mutant. Values are expressed as a percentage compared with Aβ42. Mean ± SEM of four independent experiments. *p < 0.001 (one-way ANOVA using Dunnett's post test). E, Cell viability assay performed by the MTT method. Hippocampal neurons were treated with 10 μm of AβWT, AβNTyr, and the mutant AβE14 for 24 h. Values are expressed as the percentage of the control. Mean ± SEM of 13–16 independent experiments. *p < 0.001 (one-way ANOVA using Dunnett's post test).