IMR Press / FBL / Volume 9 / Issue 6 / DOI: 10.2741/1481

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

An unconventional hypothesis of oxidation in Alzheimer's disease: intersections with excitotoxicity
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1 Departments of Geriatrics, Neurobiology & Developmental Sciences, and Internal Medicine; University of Arkansas for Medical Sciences; Little Rock AR 72205
2 Geriatric Research Education Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock AR 72205
Front. Biosci. (Landmark Ed) 2004, 9(6), 3286–3295;
Published: 1 September 2004

There are two major lines of investigation from which a connection has been traditionally drawn between chemical oxidation and Alzheimer's disease. First, a major risk factor for AD is age, and oxidative stress has long been a component of general hypotheses about biological aging. The second line of reasoning is a corollary of the Amyloid Hypothesis, the assumption that the amyloid beta-peptide (A-beta) which comprises AD's pathognomic plaques is a key mediator of the neurodegeneration occurring in this disorder. Under many experimental conditions, A-beta has been shown to evoke oxidative damage to tissues, cells, and biomolecules; even the redox properties of the peptide itself have been hotly debated. These two modalities of conjecture intersect under the Inflammatory Hypothesis of AD, as inflammation produces oxidation, old age is associated with elevation in inflammatory events, and A-beta can further exacerbate such inflammatory reactions in brain cells. This review discusses these arguments about the pathogenesis of AD and how they might be generalized to other neurodegenerative conditions. But, additional speculation is offered in the form of an inclusionary mechanism that may be specific and novel enough to qualify as a third line of theory; namely, the possibility that inflammatory reactions in microglia--activated by A-beta or other factors among the "usual suspects"--initiate programmed oxidation that is converted to the neuron-specific stress of excitotoxicity.

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