Figure 6.

Schematic model of the possible role of nitrative/oxidative modifications in the formation of PHF. Under normal conditions, tau (ovals) is in equilibrium between a free and a microtubule-bound (rectangular bars) pool, where tau stabilizes microtubules. Nitrative damage of tau may reduce its affinity for microtubules resulting in unbound nitrated (triangles) tau, which may serve as a nidus for oligomer formation, but nitration also may enhance tau fibrillization. This polymerization process can lead to the formation of complex aggregates of PHFs. o-o’ Dityrosine cross-linking (brackets) that occurs concomitantly with nitration 32 could also contribute to the stabilization of polymers.