Paula I. Moreira, Kazuhiro Honda, Quan Liu, Maria S. Santos, Catarina R. Oliveira, Gjumrakch Aliev, Akihiko Nunomura, Xiongwei Zhu, Mark A. Smith and George Perry Pages 403 - 408 ( 6 )
The complex nature and genesis of oxidative damage in Alzheimer disease can be partly answered by mitochondrial and redox-active metal abnormalities. By releasing high levels of hydrogen peroxide, dysfunctional mitochondria propagate a series of interactions between redox-active metals and oxidative response elements. In the initial phase of disease development, amyloid-β deposition and hyperphosphorylated t may function as compensatory responses and downstream adaptations to ensure that neuronal cells do not succumb to oxidative injuries. However, during the progression of the disease, the antioxidant activity of both agents evolves into pro-oxidant activity representing a typical gain-offunction transformation, which can result from an increase in reactive species and a decrease in clearance mechanisms.
alzheimer disease, amyloid-b, metal, mitochondria, oxidative stress
Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106USA.