Alzheimer disease and the role of free radicals in the pathogenesis of the disease.
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.
Moreira
Paula I
PI
Center for Neuroscience and Cell Biology of Coimbra, University of Coimbra, 3004-517 Coimbra, Portugal.
Santos
Maria S
MS
Oliveira
Catarina R
CR
Shenk
Justin C
JC
Nunomura
Akihiko
A
Smith
Mark A
MA
Zhu
Xiongwei
X
Perry
George
G
D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans
D005609:Free Radicals