|Comment by George Perry, Xiongwei Zhu, Akihiko Nunomura, Paula I. Moreira, Rudy J. Castellani, Mark A. Smith
Amyloid-β Protein Precursor at the Center of Iron and Redox Homeostasis: The Amyloid Reparative Cascade Hypothesis
It is an overused statement that the brain is poorly protected from oxidative stress. That statement is now put to rest by the elegant and meticulous work of Ashley Bush and colleagues (Duce et al., 2010). Bush has shown the amyloid-β protein precursor (AβPP) has ferroxidase activities comparable to ceruloplasmin or ferritin. Ferroxidase, by stabilizing Fe+3, is at the center of protecting cells from Fe+2/Fe+3 cycling, with consequent hydroxyl radical production. Additionally, ferroxidase activity is essential for iron transport and tissue response to injury. These findings explain why, in the face of increased oxidative damage and response, ceruloplasmin is not induced (Castellani et al., 1999). AβPP, therefore, represents a unique system, adapted to the brain, to cope with iron homeostasis. These results suggest that the iron deposits...