title: A second look into the oxidant mechanisms in Alzheimer's disease.
abstract: Oxidative damage is a major feature of Alzheimer's disease pathophysiology. Instead of succumbing to these oxidative abnormalities, neurons upregulate antioxidant defenses, which suggest a novel balance in oxidant homeostasis in Alzheimer's disease. Evidence indicates that in the initial phase of Alzheimer's disease development, amyloid-beta deposition and hyperphosphorylated tau are consequences of oxidative stress and function as a primary line of antioxidant defense. However, during the progression of the disease, the antioxidant activity of both agents evolves into pro-oxidant, representing a typical gain-of-function transformation. This transformation is due to an increase in reactive species and a decrease in clearance mechanisms. However, the notion that amyloid-beta and hyperphosphorylated tau function as protective components in the early stages of Alzheimer's disease brings into serious question the rationale of current therapeutic strategies aimed to remove both amyloid-beta and hyperphosphorylated tau.
authors.affiliation: Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA.
authors.forename: Paula I
authors.initials: PI
authors.lastname: Moreira
authors.forename: Catarina R
authors.initials: CR
authors.lastname: Oliveira
authors.forename: Maria S
authors.initials: MS
authors.lastname: Santos
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nunomura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Honda
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 / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D016875:tau Proteins