title: Oxidative stress: the old enemy in Alzheimer's disease pathophysiology.
abstract: 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.
authors.affiliation: Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
authors.forename: Paula I
authors.initials: PI
authors.lastname: Moreira
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Honda
authors.forename: Quan
authors.initials: Q
authors.lastname: Liu
authors.forename: Maria S
authors.initials: MS
authors.lastname: Santos
authors.forename: Catarina R
authors.initials: CR
authors.lastname: Oliveira
authors.forename: Gjumrakch
authors.initials: G
authors.lastname: Aliev
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nunomura
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: George
authors.initials: G
authors.lastname: Perry
mesh_terms: 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*
chemical_list: D008670:Metals