Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid beta-peptide
ABSTRACT Amyloid beta-peptide (Abeta) is heavily deposited in the brains of Alzheimer's disease (AD) patients. Free-radical oxidative stress, particularly of neuronal lipids, proteins and DNA, is extensive in those AD brain areas in which Abeta is abundant. Recent research suggests that these observations might be linked, and it is postulated that Abeta-induced oxidative stress leads to neurodegeneration in AD brain. Consonant with this postulate, Abeta leads to neuronal lipid peroxidation, protein oxidation and DNA oxidation by means that are inhibited by free-radical antioxidants. Here, we summarize current research on phospholipid peroxidation, as well as protein and DNA oxidation, in AD brain, and discuss the potential role of Abeta in this oxidative stress.
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ABSTRACT: Neurodegenerative diseases including Alzheimer (AD) and Parkinson (PD) have attracted attention in last decades due to their high incidence worldwide. The etiology of these diseases is still unclear; however the role of the environment as a putative risk factor has gained importance. More worryingly is the evidence that pre-and post-natal exposures to environmental factors predispose to the onset of neurodegenerative diseases in later life. Neurotoxic metals such as lead, mercury, aluminum, cadmium and arsenic, as well as some pesticides and metal-based nanoparticles have been involved in AD due to their ability to increase beta-amyloid (Aβ) peptide and the phosphorylation of Tau protein (P-Tau), causing senile/amyloid plaques and neurofibrillary tangles (NFTs) characteristic of AD. The exposure to lead, manganese, solvents and some pesticides has been related to hallmarks of PD such as mitochondrial dysfunction, alterations in metal homeostasis and aggregation of proteins such as α-synuclein (α-syn), which is a key constituent of Lewy bodies (LB), a crucial factor in PD pathogenesis. Common mechanisms of environmental pollutants to increase Aβ, P-Tau, α-syn and neuronal death have been reported, including the oxidative stress mainly involved in the increase of Aβ and α-syn, and the reduced activity/protein levels of Aβ degrading enzyme (IDE)s such as neprilysin or insulin IDE. In addition, epigenetic mechanisms by maternal nutrient supplementation and exposure to heavy metals and pesticides have been proposed to lead phenotypic diversity and susceptibility to neurodegenerative diseases. This review discusses data from epidemiological and experimental studies about the role of environmental factors in the development of idiopathic AD and PD, and their mechanisms of action.Frontiers in Cellular Neuroscience 05/2015; 9. DOI:10.3389/fncel.2015.00124 · 4.18 Impact Factor
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ABSTRACT: Objective Haptoglobin (Hpg) is known to have several functional properties, including antioxidant and anti-inflammatory activities. In addition, it has been shown that the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD), involves inflammation as well as oxidative stress. However, evidence suggesting an association between the serum Hpg level and AD is lacking. Therefore, we conducted this study in order to investigate whether serum Hpg is associated with AD. Methods We compared the serum Hpg levels of 121 patients with newly diagnosed AD, 58 patients with Parkinson's disease (PD) and 43 healthy controls. We also evaluated the relationship between the severity of cognitive impairment in patients with AD and the serum Hpg level. Results The mean serum Hpg level of the patients with AD was significantly higher than that of the healthy controls (p=0.042), although it was not significant different from that observed in the PD group (p=0.613). We also found a significant positive association between the serum Hpg level and the severity of cognitive impairment, as measured using several neuropsychological tests, in the patients with AD. The odds ratio (95% confidence interval) of the patients with AD grouped according to the Hpg level was 2.417 (95% confidence interval=1.134-5.149). Conclusion We observed a significantly higher mean serum Hpg level among the patients with AD compared to the healthy controls. These results support the hypothesis that oxidative stress and neuroinflammatory reactions play a role in the pathogenesis of AD.Internal Medicine 01/2015; 54(5):453-7. DOI:10.2169/internalmedicine.54.2876 · 0.97 Impact Factor
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ABSTRACT: [in Russian] The monograph is devoted to the generalization of the existing synthetic methods of the nanoceria and the analysis of the physical, chemical properties and biological activity of nanosized cerium dioxide. The results of the work carried out with the participation of the authors of the monograph, as well as literature data were critically analyzed. The main attention is focused on the results obtained in the last 5-10 years. The questions of the formation and growth of ceria nanoparticles in different environments are studied, the data on the structural characteristics of the material, its toxicity, mechanism of action on living systems and protection against oxidative stress, the influence on the prolongation of lifespan, healthy aging and antiviral activity etc. are critically discussed. The monograph is intended for researchers working in the field of inorganic materials science and nanobiotechnology, as well as graduate and undergraduate students. [in Russian]Edited by N.Y. Spivak, Yu.D. Tretyakov, 07/2013; Publishing house of University of Tomsk., ISBN: 978-5-7511-2182-2