Reactive Oxygen Species Mediate Cellular Damage in Alzheimer Disease

Abstract

ABSTRACT:The two most striking features of Alzheimer disease are (i) the multitude of abnormalities affecting essentially every system and (ii) the strict age dependence. Recent work suggests that both features are linked to increased oxidative stress that damages lipids, proteins and nucleic acids and results in redox-active metal accumulations, mitochondrial damage and formation of advanced glycation endproducts.Interestingly, β-protein precursor, amyloid-β, presenilins, and apolipoprotein E have all been linked to reactive oxygen species production or apoptosis, a process intimately associated with oxidative stress. In therapeutics, the commonality between a number of efficacious agents appears to be oxidative stress reduction. Therefore, we contend that oxidative stress is the element that links the multitude of changes in Alzheimer disease and that a reduction of oxidative stress will have a dramatic effect on reducing the incidence or progression of Alzheimer disease.

Dietary resveratrol prevents Alzheimer’s markers and increases life span in SAMP8

“…It is plausible to hypothesize that, although long-term treatment by resveratrol prevents tau hyperphosphorylation, detectable by specific phospho-antibodies, the inhibition of intermediate signals under these conditions is lost because of the chronicity of the treatment. On the other hand, oxidative stress is a well-established pathogenic factor in AD (Smith et al 1995;Markesbery 1997;Perry et al 1998), and the association of oxidative stress with tau abnormalities is well-known. As such, the resveratrol-driven reductions on tau phosphorylation in the hippocampus could be mediated by the well-known antioxidant effects of this polyphenol rather than through its inhibitory effect on tau kinases.…”

Paeonol increases levels of cortical cytochrome oxidase and vascular actin and improves behavior in a rat model of Alzheimer's disease

“…Injection of Aβ peptides into the hippocampus of animals is a commonly used method to establish an AD animal model (Pike et al, 1997;Perry et al, 1998). Many studies have described parallels between the presence of endogenous Aβ1-42 and the administered peptide and the ability of either, to induce lesions and promote the pathological changes resembling those associated with AD (Zhang et al, 2006).…”

Lipoic Acid and N-acetyl Cysteine Decrease Mitochondrial-Related Oxidative Stress in Alzheimer Disease Patient Fibroblasts

“…An accumulating body of knowledge suggests that oxidative stress, and subsequent oxidative damage [55,57] occurs early in the progression of AD, significantly before the development of the pathologic hallmarks, neurofibrillary tangles and senile plaques [50][51][52]71]. In diseased neurons the interaction of abnormal mitochondria, redox transition metals, and oxidative stress response elements contributes to the generation of ROS [55].…”

“…The processes underlying the pathology of AD involve several factors, including mitochondrial dysfunction, abnormal protein aggregation, metal accumulation, inflammation and ex-citotoxicity. Although the relationship between these factors and the development of AD is multidirectional, oxidative damage is considered a common thread linking some of these factors [40,55].…”