title: Alzheimer disease and the role of free radicals in the pathogenesis of the disease.
abstract: Oxidative stress occurs early in the progression of Alzheimer disease, significantly before the development of the pathologic hallmarks, neurofibrillary tangles and senile plaques. All classes of macromolecules (sugar, lipids, proteins, and nucleic acids) are affected by oxidative stress leading, inevitably, to neuronal dysfunction. Extensive data from the literature support the notion that mitochondrial and metal abnormalities are key sources of oxidative stress in Alzheimer disease. Furthermore, it has been suggested that in the initial stages of the development of Alzheimer disease, amyloid-beta deposition and hyperphosphorylated tau function as compensatory responses to ensure that neuronal cells do not succumb to oxidative damage. However, during the progression of the disease, the antioxidant activity of both agents is either overwhelmed or, according to others, evolves into pro-oxidant activity resulting in the exacerbation of reactive species production.
authors.affiliation: Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Paula I
authors.initials: PI
authors.lastname: Moreira
authors.forename: Maria S
authors.initials: MS
authors.lastname: Santos
authors.forename: Catarina R
authors.initials: CR
authors.lastname: Oliveira
authors.forename: Justin C
authors.initials: JC
authors.lastname: Shenk
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nunomura
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Zhu
authors.forename: George
authors.initials: G
authors.lastname: Perry
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans
chemical_list: D005609:Free Radicals