Oxidative stress: the old enemy in Alzheimer's disease pathophysiology.
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-beta deposition and hyperphosphorylated tau 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-of-function transformation, which can result from an increase in reactive species and a decrease in clearance mechanisms.
Moreira
Paula I
PI
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Honda
Kazuhiro
K
Liu
Quan
Q
Santos
Maria S
MS
Oliveira
Catarina R
CR
Aliev
Gjumrakch
G
Nunomura
Akihiko
A
Zhu
Xiongwei
X
Smith
Mark A
MA
Perry
George
G
D000544:Alzheimer Disease / Q000503:physiopathology*; D000818:Animals; D006801:Humans; D008670:Metals / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*
D008670:Metals