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Role of oxidative stress in Alzheimer's disease (Review)

  • Authors:
    • Wen‑Juan Huang
    • Xia Zhang
    • Wei‑Wei Chen
  • View Affiliations

  • Published online on: March 15, 2016
  • Pages: 519-522
  • Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Alzheimer's disease (AD) is the most common cause of disability in individuals aged >65 years worldwide. AD is characterized by the abnormal deposition of amyloid β (Aβ) peptide, and intracellular accumulation of neurofibrillary tangles of hyperphosphorylated τ protein and dementia. The neurotoxic oligomer Aβ peptide, which is the neuropathological diagnostic criterion of the disease, together with τ protein, are mediators of the neurodegeneration that is among the main causative factors. However, these phenomena are mainly initiated and enhanced by oxidative stress, a process referring to an imbalance between antioxidants and oxidants in favour of oxidants. This imbalance can occur as a result of increased free radicals or a decrease in antioxidant defense, free radicals being a species that contains one or more unpaired electrons in its outer shell. The major source of potent free radicals is the reduction of molecular oxygen in water, that initially yields the superoxide radical, which produces hydrogen peroxide by the addition of an electron. The reduction of hydrogen peroxide produces highly reactive hydroxyl radicals, termed reactive oxygen species (ROS) that can react with lipids, proteins, nucleic acids, and other molecules and may also alter their structures and functions. Thus, tissues and organs, particularly the brain, a vulnerable organ, are affected by ROS due to its composition. The brain is largely composed of easily oxidizable lipids while featuring a high oxygen consumption rate. The current review examined the role of oxidative stress in AD.


Oxidative stress, a process increased in the brain with aging, is induced by an imbalance in the redox state, involving the generation of excess reactive oxygen species (ROS) or the dysfunction of the antioxidant system (1). The mitochondrial electron transport chain consumes almost 98% of molecular oxygen at the cytochrome oxidase complex and the remaining oxygen is reduced to hydrogen peroxide and superoxide radicals. During normal metabolism and various functions the oxygen radical superoxide (O2•−) and the non-radical oxidant hydrogen peroxide (H2O2) and hypochlorous acid are produced (2). When the production of (O2•−) and (H2O2) becomes excessive, they can result in tissue damage that often involves the generation of the highly reactive hydroxyl radical (OH) and other oxidant molecules in the presence of catalytic iron or copper ions (3). Accordingly, since metal catalyzes redox reactions (3), one of the major forms of antioxidant defense consists of storing and transporting the iron in forms that do not catalyse the formation of reactive radicals (4), as is the case during tissue injury, in which there is an increase in iron availability that can accelerate free radical reactions (4).

Although it is rich in biometals and lipids, the brain has abundantly peroxidation-susceptible lipid cells and is an organ with a high demand for oxygen (5). Additionally, the cerebrospinal fluid cannot bind released iron ions (5). Consequently, oxidative stress on nervous tissue may seriously damage the brain via several interacting mechanisms, including an increase in intracellular free Ca2+, release of excitatory amino acids, and neurotoxicity (5,6). Other important sources or modulators of oxidative stress, include reactive nitrogen species (RNS), including nitric oxide (NO) and peroxynitrite which can particularly be extremely reactive with proteins, lipids, nucleic acid and other molecules in further altering structure and/or functionalities leading to detrimental effects for the brain (79). Cells with an accumulation of oxidized products such as aldehydes and isoprostanes, protein carbonyls, and base adducts from DNA oxidation can be seriously altered (10). Consequently, the considerable ROS formation increased by the electron transport system within the mitochondria under stressful conditions and in aging constitutes a risk for developing Alzheimer's disease (AD), when no efficient antioxidant system is available. Thus, mitochondria function as both the source and target of toxic ROS since mitochondrial dysfunction and oxidative stress are important in aging and neurodegenerative diseases, particularly AD (11,12).

This late-onset and sporadic illness affects mostly individuals >65 years worldwide (13) and is characterized by the abnormal deposition of the amyloid β (Aβ) peptide, intracellular accumulation of neurofibrillary tangles of hyperphosphorylated τ protein, loss of synapses and dendritic spines, cholinergic denervation, hypoperfusion and hyperemia (14). The neurotoxic oligomer Aβ peptide (15), which is the neuropathological diagnostic criterion of the disease, together with τ protein, constitute mediators of neurodegeneration, which is among the main causative factors of impaired synaptic plasticity, neuroinflammation, part of vascular reactivity impairment, cholinergic denervation, neurotransmitter imbalance, neuronal loss, dendritic alterations and substantial synaptic loss (16) through oxidative stress (17). Mechanisms by which mitochondrial dysfunction leads to neuron degeneration in AD are believed to be associated with ROS generation, activation of mitochondrial permeability transition, excitotoxicity, impaired production of adenosine triphosphate and altered calcium homeostasis (18). They suggest a pivotal role for oxidative stress in the pathophysiology of AD, which is the focus of the current review.

Oxidative stress

Oxidative stress encompasses a variety of molecules and free radicals deriving from molecular oxygen. These free radicals are chemical species carrying one unpaired electron in the outer shell (1). Molecular oxygen in the ground state is a bi-radical with two single electrons in the outer shell, sharing the same spin. Accordingly, since the oxygen molecule is able to react with one electron at a time, oxygen is not extremely reactive with the electrons in a chemical bond (1). Therefore, when one of the two electrons is excited it spins. The two electrons exhibit opposing spins and are able to quickly react with other pairs of electrons, particularly double bonds. The resulting singlet oxygen becomes a powerful oxidant (19). The reduction of oxygen by one electron produces fairly stable intermediates leading to the formation of a superoxide anion (O2•−), the precursor of most ROS and mediator in oxidative stress chain reactions. Additionally, O2•− is partially reduced by antioxidants to a hydroxyl radical (OH), one of the strongest oxidants in nature. This reaction is catalysed by reduced transition metals, which in turn may be reduced again by O2•− thereby propagating the process (19). Furthermore, O2•− also reacts with other radicals such as NO under the control of the rate of diffusion of the two radicals and results in the formation of peroxynitrite (20), which is an extremely powerful oxidant driving oxidants termed RNS (21,22). Accordingly, ROS and/or RNS constitute the main players, which in the presence of limited antioxidant defences induce oxidative stress. ROS and/or RNS have a dual role in intracellular signalling, cell proliferation and survival (23,24). However, when a slight fluctuation in the steady-state concentration becomes uncontrolled it may lead to increases in the steady-state concentration, resulting in free radical-mediated chain reactions that indiscriminately target lipids (25), proteins (26), polysaccharides (27) and even DNA (28,29).

However, as mentioned above, in vivo O2•− is produced by mitochondria, under the control of enzymatic and non-enzymatic processes (30). The mitochondria electron transport chain contains a number of redox centres that leak electrons to oxygen, and contains the main sources of O2•− in the majority of tissues (30,31). Thus, the major enzymatic sources of O2•− are NADPH oxidases located in various cell membranes, including polymorphonuclear, macrophages and endothelial cells (3234), as well as cytochrome P450•− and H2O2-dependent oxygenases (35,36). Another enzymatic source of O2•− as a source of OH is the proteolytic conversion of xanthine dehydrogenase to xanthine oxidase (37). The non-enzymatic production of O2•− occurs via the direct transfer of oxygen by reduced coenzymes or prosthetic groups, such as flavin, iron sulfur clusters, or by xenobiotics after a previous reduction by enzymes, including anticancer agents or herbicides (38).

However, mitochondria also prevent ROS and regulate the steady-state concentration of O2•− in the intermembrane space by three different mechanisms. The first mechanism involves the enzyme superoxide dismutase (SOD) (39), acting through the dismutation of O2 and producing hydrogen peroxide (H2) in fully reduced water product. There are two types of SOD including the specific mitochondrial matrix containing the manganese active site (40) (MnSOD or SOD2), which eliminates O2•− formed in the matrix or on the inner side of the inner membrane, and SOD containing copper and zinc (41) instead of manganese SOD (copper-zinc SOD or SOD1) located in the cytoplasm of eukaryotic cells. The second mechanism is associated with cytochrome c in the intermembrane space that can reduce O2•− (42) to regenerate oxygen in the process (43), glutathione peroxidase which mostly decomposes O2•− and OH (44), and catalase, the major detoxifying enzyme identified in peroxisomes (45). Ubiquinol (QH2) is another carrier appearing to have a detoxifying role against ROS, acting as a reducing agent in the elimination of various peroxides in the presence of succinate (46). The mitochondrion also has a variety of DNA-repairing enzymes that correct errors resulting from O2 damage, since the mitochondrial chromosome contains 5% (vs. 95% encoded by nuclear DNA) of genes from several important proteins such as the subunits of nicotinamide adenine dinucleotide dehydrogenase and cytochrome oxidase and cytochrome b (9).

Therefore, under normal conditions, there is a balance between ROS formation and antioxidant. This equilibrium is disrupted during several pathological scenarios in which the antioxidant defences become insufficient, resulting in oxidative stress often leading to apoptosis, a mechanism used by organisms to eliminate redundant or damaged cells (47), and/or cell death.

Role of oxidative stress in Alzheimer's disease

The brain of patients suffering AD present a significant extent of oxidative damage associated with the abnormal marked accumulation of Aβ and the deposition of neurofibrillary tangles (48). Mounting evidence suggests an important role played by biometals including iron, zinc and copper in Aβ and neurodegeneration (49). In concordance with those findings, there are high affinity binding sites for copper and zinc on the N-terminal metal-binding domains of Aβ and its precursor APP (50,51) while copper is a potent mediator of the highly reactive hydroxyl radical (OH), and consequently contributes to the increase of oxidative stress characteristic of AD brain (52) according to the high concentration of copper found in amyloid plaques (53). This seems to be associated with the length of Aβ fragments, with Aβ (142) being more toxic than Aβ (140) and the most likely candidate to generate hydrogen peroxide and other ROS (54). In addition, high concentrations of zinc were associated with memory and cognitive regions of the brain, including the neocortex and amygdala, and hippocampus, which are mostly affected in AD pathology (55,56). This binding of zinc has a highly ordered conformational state of Aβ (140), leading to the production of toxic, fibrillary, Aβ aggregates. Consequently, the immunological/inflammatory response to non-soluble Aβ plaques involves the disruption of zinc homeostasis followed by uncontrolled cerebral zinc release, which is typical for oxidative stress. Thus, the uncontrolled accumulation of zinc or Aβ leads to zinc-induced and Aβ-mediated oxidative stress and cytotoxicity (57).

Therefore, whereas the brain membrane phospholipids are composed of polyunsaturated fatty acids, this organ is particularly vulnerable to free radical attacks. Their double binds allow the removal of hydrogen ions (58) and increased lipid peroxidation, which is the most prominent feature in which degenerative change is most pronounced in the AD brain (59). In addition, the oxidation of proteins by free radicals may be significant in AD as the oxidation of brain proteins can affect enzymes critical to neuron and glial functions. This is the case for two enzymes especially sensitive to oxidative modification, that of glutamine synthetase and creatine kinase, which are markedly reduced in AD brains (60), reflecting the alteration of glutamate concentrations and enhancement of excitotoxicity, whereas oxidative impairment of creatine kinase may cause decreased energy metabolism in AD (61). The pathologic aggregation of protein leads to fibril formation and insolubility (62). Thus, neurofibrillary tangles are characterized by the aggregation and hyperphosphorylation of the τ protein into paired helical filaments. Phosphorylation is linked to oxidation through the microtubule-associated protein kinase pathway and through activation of the transcription factor nuclear factor-κB, thus potentially linking oxidation to the hyperphosphorylation of τ proteins (63). Protein oxidation is also capable of inducing advanced glycation end products as a post-translational modification of proteins that are formed when amino group of proteins react non-enzymatically with monosaccharides (64). Furthermore, oxidation of the brain can affect DNA, producing strand breaks, sister chromatid exchange, DNA-protein crosslinking, and base modification (65).

Thus, the overproduction of ROS resulting in oxidative stress may have a deleterious effect and can be an important mediator of damage to cell structures and consequently various disease states and aging. However, antioxidant treatments have demonstrated that AD is associated with oxidative stress, being a more complex disease.


Although AD is probably associated with multiple etiologies and pathophysiologic mechanisms, oxidative stress appears as a major part of the pathophysiologic process. Accordingly, the mitochondrial respiratory chain constitutes the main intracellular source of ROS in most tissues. The resulting oxidants are maintained at a non-toxic steady-state concentration by a variety of antioxidant defences and repair enzymes. The delicate balance of oxidants/antioxidants defences and ROS production may be disrupted by deficient antioxidant defences, inhibition of electron flow or exposure to xenobiotics, becoming the common denominator in pathological processes associated with oxidative insult leading to tissue damage and/or death. Therefore, changes in the balance of redox transition metal, particularly of iron and copper are crucial. This is a significant role for oxidative brain in AD since the brain is vulnerable to oxidative stress. However, multicenter trials support the capacity of antioxidant treatment effects in the retardation of the progression of AD, suggesting the complexity of AD. Additional studies are required to gain a better understanding of the disease.



Andreyev AY, Kushnareva YE and Starkov AA: Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc). 70:200–214. 2005. View Article : Google Scholar : PubMed/NCBI


Leeuwenburgh C and Heinecke JW: Oxidative stress and antioxidants in exercise. Curr Med Chem. 8:829–838. 2001. View Article : Google Scholar : PubMed/NCBI


Sheldon RA: Metal-catalyzed oxidations of organic compounds: mechanistic principles and synthetic methodology including biochemical processes. Elsevier. New York, NY: 2012.


Valko M, Rhodes CJ, Moncol J, Izakovic M and Mazur M: Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 160:1–40. 2006. View Article : Google Scholar : PubMed/NCBI


Halliwell B: Reactive oxygen species and the central nervous system. Free radicals in the brain. Springer Berlin Heidelberg. (New York, NY). 21–40. 1992. View Article : Google Scholar


Bambrick L, Kristian T and Fiskum G: Astrocyte mitochondrial mechanisms of ischemic brain injury and neuroprotection. Neurochem Res. 29:601–608. 2004. View Article : Google Scholar : PubMed/NCBI


Lee J, Koo N and Min D: Reactive oxygen species, aging, and antioxidative nutraceuticals. Compr Rev Food Sci Food Saf. 3:21–33. 2004. View Article : Google Scholar


Smith KJ, Kapoor R and Felts PA: Demyelination: The role of reactive oxygen and nitrogen species. Brain Pathol. 9:69–92. 1999. View Article : Google Scholar : PubMed/NCBI


Turrens JF: Mitochondrial formation of reactive oxygen species. J Physiol. 552:335–344. 2003. View Article : Google Scholar : PubMed/NCBI


Dalle-Donne I, Rossi R, Giustarini D, Milzani A and Colombo R: Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta. 329:23–38. 2003. View Article : Google Scholar : PubMed/NCBI


Clarke JR, Lyra E, Silva NM, Figueiredo CP, Frozza RL, Ledo JH, Beckman D, Katashima CK, Razolli D, Carvalho BM, Frazão R, et al: Alzheimer-associated Aβ oligomers impact the central nervous system to induce peripheral metabolic deregulation. EMBO Mol Med. 7:190–210. 2015. View Article : Google Scholar : PubMed/NCBI


Beal MF: Mitochondrial dysfunction in neurodegenerative diseases. Biochim Biophys Acta. 1366:211–223. 1998. View Article : Google Scholar : PubMed/NCBI


Kumar A, Singh A and Ekavali: A review on Alzheimer's disease pathophysiology and its management: An update. Pharmacol Rep. 67:195–203. 2015. View Article : Google Scholar : PubMed/NCBI


Harkany T, Penke B and Luiten PG: β-Amyloid excitotoxicity in rat magnocellular nucleus basalis. Effect of cortical deafferentation on cerebral blood flow regulation and implications for Alzheimer's disease. Ann N Y Acad Sci. 903:374–386. 2000. View Article : Google Scholar : PubMed/NCBI


Walsh DM and Selkoe DJ: Aβ oligomers - a decade of discovery. J Neurochem. 101:1172–1184. 2007. View Article : Google Scholar : PubMed/NCBI


Gelain DP, Antonio Behr G, de Oliveira Birnfeld R and Trujillo M: Antioxidant therapies for neurodegenerative diseases: mechanisms, current trends, and perspectives. Oxid Med Cell Longev. 2012:8951532012. View Article : Google Scholar : PubMed/NCBI


Varadarajan S, Yatin S, Aksenova M and Butterfield DA: Review: Alzheimer's amyloid β-peptide-associated free radical oxidative stress and neurotoxicity. J Struct Biol. 130:184–208. 2000. View Article : Google Scholar : PubMed/NCBI


Parker WD Jr and Davis RE: Primary mitochondrial DNA defects as a causative event in Alzheimer's disease. Mitochondria and free radicals in neurodegenerative diseases. Beal MF, Howell N and Bodis-Wollner I: Wiley-Liss. (New York, NY). 319–333. 1997.


Liochev SI and Fridovich I: Superoxide and iron: Partners in crime. IUBMB Life. 48:157–161. 1999. View Article : Google Scholar : PubMed/NCBI


Hebelstrup KH and Møller IM: Mitochondrial signaling in plants under hypoxia: Use of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Reactive oxygen and nitrogen species signaling and communication in plants. Gupta KJ and Igamberdiev AU: 23:Springer International Publishing. (Switzerland). 63–77. 2015.


Zhang X and Gao F: Imaging mitochondrial reactive oxygen species with fluorescent probes: Current applications and challenges. Free Radic Res. 49:374–382. 2015. View Article : Google Scholar : PubMed/NCBI


Reeg S and Grune T: Protein oxidation in toxicology. Studies on experimental toxicology and pharmacology. Springer International Publishing. (Switzerland). 81–102. 2015. View Article : Google Scholar


Dröge W: Free radicals in the physiological control of cell function. Physiol Rev. 82:47–95. 2002. View Article : Google Scholar : PubMed/NCBI


Panieri E and Santoro MM: ROS signaling and redox biology in endothelial cells. Cell Mol Life Sci. 72:3281–3303. 2015. View Article : Google Scholar : PubMed/NCBI


Rubbo H, Radi R, Trujillo M, Telleri R, Kalyanaraman B, Barnes S, Kirk M and Freeman BA: Nitric oxide regulation of superoxide and peroxynitrite-dependent lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. J Biol Chem. 269:26066–26075. 1994.PubMed/NCBI


Stadtman ER and Levine RL: Protein oxidation. Ann N Y Acad Sci. 899:191–208. 2000. View Article : Google Scholar : PubMed/NCBI


Kaur H and Halliwell B: Evidence for nitric oxide-mediated oxidative damage in chronic inflammation. Nitrotyrosine in serum and synovial fluid from rheumatoid patients. FEBS Lett. 350:9–12. 1994. View Article : Google Scholar : PubMed/NCBI


Cheeseman KH and Slater TF: An introduction to free radical biochemistry. Br Med Bull. 49:481–493. 1993.PubMed/NCBI


Mustafa SA, Karieb SS, Davies SJ and Jha AN: Assessment of oxidative damage to DNA, transcriptional expression of key genes, lipid peroxidation and histopathological changes in carp Cyprinus carpio L. following exposure to chronic hypoxic and subsequent recovery in normoxic conditions. Mutagenesis. 30:107–116. 2015. View Article : Google Scholar : PubMed/NCBI


Therade-Matharan S, Laemmel E, Duranteau J and Vicaut E: Reoxygenation after hypoxia and glucose depletion causes reactive oxygen species production by mitochondria in HUVEC. Am J Physiol Regul Integr Comp Physiol. 287:R1037–R1043. 2004. View Article : Google Scholar : PubMed/NCBI


Hwang HJ, Lynn SG, Vengellur A, Saini Y, Grier EA, Ferguson-Miller SM and LaPres JJ: Hypoxia inducible factors modulate mitochondrial oxygen consumption and transcriptional regulation of nuclear-encoded electron transport chain genes. Biochemistry. 54:3739–3748. 2015. View Article : Google Scholar : PubMed/NCBI


Babior BM: Phagocytes and oxidative stress. Am J Med. 109:33–44. 2000. View Article : Google Scholar : PubMed/NCBI


Babior BM: The NADPH oxidase of endothelial cells. IUBMB Life. 50:267–269. 2000. View Article : Google Scholar : PubMed/NCBI


Vignais PV: The superoxide-generating NADPH oxidase: Structural aspects and activation mechanism. Cell Mol Life Sci. 59:1428–1459. 2002. View Article : Google Scholar : PubMed/NCBI


Coon MJ, Ding XX, Pernecky SJ and Vaz AD: Cytochrome P450: Progress and predictions. FASEB J. 6:669–673. 1992.PubMed/NCBI


Hlavica P: Mechanistic basis of electron transfer to cytochromes P450 by natural redox partners and artificial donor constructs. Monooxygenase, peroxidase and peroxygenase properties and mechanisms of cytochrome P450. Hrycay EG and Bandiera SM: 851:Springer International Publishing. (Switzerland). 247–297. 2015. View Article : Google Scholar


Yokoyama Y, Beckman JS, Beckman TK, Wheat JK, Cash TG, Freeman BA and Parks DA: Circulating xanthine oxidase: Potential mediator of ischemic injury. Am J Physiol. 258:G564–G570. 1990.PubMed/NCBI


Kehrer JP: Free radicals as mediators of tissue injury and disease. Crit Rev Toxicol. 23:21–48. 1993. View Article : Google Scholar : PubMed/NCBI


Corvo ML, Marinho HS, Marcelino P, Lopes RM, Vale CA, Marques CR, Martins LC, Laverman P, Storm G and Martins MBA: Superoxide dismutase enzymosomes: Carrier capacity optimization, in vivo behaviour and therapeutic activity. Pharm Res. 32:91–102. 2015. View Article : Google Scholar : PubMed/NCBI


Fridovich I: Superoxide radical and superoxide dismutases. Annu Rev Biochem. 64:97–112. 1995. View Article : Google Scholar : PubMed/NCBI


Okado-Matsumoto A and Fridovich I: Subcellular distribution of superoxide dismutases (SOD) in rat liver: Cu, Zn-SOD in mitochondria. J Biol Chem. 276:38388–38393. 2001. View Article : Google Scholar : PubMed/NCBI


Butler J, Koppenol WH and Margoliash E: Kinetics and mechanism of the reduction of ferricytochrome c by the superoxide anion. J Biol Chem. 257:10747–10750. 1982.PubMed/NCBI


Marí M, Morales A, Colell A, García-Ruiz C and Fernandez-Checa JC: Oxidative stress in nonalcoholic fatty liver disease. Studies on hepatic disorders. Albano E and Parola M: Springer International Publishing. (Switzerland). 279–308. 2015.


Wang T, Lu W, Lu S and Kong J: Protective role of glutathione against oxidative stress in Streptococcus thermophilus. Int Dairy J. 45:41–47. 2015. View Article : Google Scholar


Finkel T and Holbrook NJ: Oxidants, oxidative stress and the biology of ageing. Nature. 408:239–247. 2000. View Article : Google Scholar : PubMed/NCBI


Aboul-Fotouh S: Coenzyme Q10 displays antidepressant-like activity with reduction of hippocampal oxidative/nitrosative DNA damage in chronically stressed rats. Pharmacol Biochem Behav. 104:105–112. 2013. View Article : Google Scholar : PubMed/NCBI


Hoeberichts FA and Woltering EJ: Multiple mediators of plant programmed cell death: Interplay of conserved cell death mechanisms and plant-specific regulators. BioEssays. 25:47–57. 2003. View Article : Google Scholar : PubMed/NCBI


Christen Y: Oxidative stress and Alzheimer disease. Am J Clin Nutr. 71:621S–629S. 2000.PubMed/NCBI


Kozlowski H, Janicka-Klos A, Brasun J, Gaggelli E, Valensin D and Valensin G: Copper, iron, and zinc ions homeostasis and their role in neurodegenerative disorders (metal uptake, transport, distribution and regulation). Coord Chem Rev. 253:2665–2685. 2009. View Article : Google Scholar


Barnham KJ, McKinstry WJ, Multhaup G, Galatis D, Morton CJ, Curtain CC, Williamson NA, White AR, Hinds MG, Norton RS, et al: Structure of the Alzheimer's disease amyloid precursor protein copper binding domain. A regulator of neuronal copper homeostasis. J Biol Chem. 278:17401–17407. 2003. View Article : Google Scholar : PubMed/NCBI


Miura T, Suzuki K, Kohata N and Takeuchi H: Metal binding modes of Alzheimer's amyloid β-peptide in insoluble aggregates and soluble complexes. Biochemistry. 39:7024–7031. 2000. View Article : Google Scholar : PubMed/NCBI


Valko M, Morris H and Cronin MT: ValkoM: Metals, toxicity and oxidative stress. Curr Med Chem. 12:1161–1208. 2005. View Article : Google Scholar : PubMed/NCBI


Strozyk D, Launer LJ, Adlard PA, Cherny RA, Tsatsanis A, Volitakis I, Blennow K, Petrovitch H, White LR and Bush AI: Zinc and copper modulate Alzheimer Abeta levels in human cerebrospinal fluid. Neurobiol Aging. 30:1069–1077. 2009. View Article : Google Scholar : PubMed/NCBI


Butterfield DA: Amyloid β-peptide (1–42)-induced oxidative stress and neurotoxicity: Implications for neurodegeneration in Alzheimer's disease brain. A review. Free Radic Res. 36:1307–1313. 2002. View Article : Google Scholar : PubMed/NCBI


Huang X, Moir RD, Tanzi RE, Bush AI and Rogers JT: Redox-active metals, oxidative stress, and Alzheimer's disease pathology. Ann N Y Acad Sci. 1012:153–163. 2004. View Article : Google Scholar : PubMed/NCBI


Cuajungco MP and Fagét KY: Zinc takes the center stage: Its paradoxical role in Alzheimer's disease. Brain Res Brain Res Rev. 41:44–56. 2003. View Article : Google Scholar : PubMed/NCBI


Pal A, Badyal RK, Vasishta RK, Attri SV, Thapa BR and Prasad R: Biochemical, histological, and memory impairment effects of chronic copper toxicity: A model for non-Wilsonian brain copper toxicosis in Wistar rat. Biol Trace Elem Res. 153:257–268. 2013. View Article : Google Scholar : PubMed/NCBI


Tsaluchidu S, Cocchi M, Tonello L and Puri BK: Fatty acids and oxidative stress in psychiatric disorders. BMC Psychiatry. 8(Suppl 1): S52008. View Article : Google Scholar : PubMed/NCBI


Markesbery WR: Oxidative stress hypothesis in Alzheimer's disease. Free Radic Biol Med. 23:134–147. 1997. View Article : Google Scholar : PubMed/NCBI


Butterfield DA, Hensley K, Cole P, Subramaniam R, Aksenov M, Aksenova M, Bummer PM, Haley BE and Carney JM: Oxidatively induced structural alteration of glutamine synthetase assessed by analysis of spin label incorporation kinetics: Relevance to Alzheimer's disease. J Neurochem. 68:2451–2457. 1997. View Article : Google Scholar : PubMed/NCBI


Moreira PI, Honda K, Liu Q, Aliev G, Oliveira CR, Santos MS, Zhu X, Smith MA and Perry G: Alzheimer's disease and oxidative stress: The old problem remains unsolved. Curr Med Chem Cent Nerv Syst Agents. 5:51–62. 2005. View Article : Google Scholar


Koo EH, Lansbury PT Jr and Kelly JW: Amyloid diseases: Abnormal protein aggregation in neurodegeneration. Proc Natl Acad Sci USA. 96:9989–9990. 1999. View Article : Google Scholar : PubMed/NCBI


Markesbery WR: The role of oxidative stress in Alzheimer disease. Arch Neurol. 56:1449–1452. 1999. View Article : Google Scholar : PubMed/NCBI


Dawnay AB and Millar DJ: Glycation and advanced glycation end-product formation with icodextrin and dextrose. Perit Dial Int. 17:52–58. 1997.PubMed/NCBI


Cooke MS, Evans MD, Dizdaroglu M and Lunec J: Oxidative DNA damage: Mechanisms, mutation, and disease. FASEB J. 17:1195–1214. 2003. View Article : Google Scholar : PubMed/NCBI

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Huang WJ, Zhang X and Chen WW: Role of oxidative stress in Alzheimer's disease (Review). Biomed Rep 4: 519-522, 2016
Huang, W., Zhang, X., & Chen, W. (2016). Role of oxidative stress in Alzheimer's disease (Review). Biomedical Reports, 4, 519-522.
Huang, W., Zhang, X., Chen, W."Role of oxidative stress in Alzheimer's disease (Review)". Biomedical Reports 4.5 (2016): 519-522.
Huang, W., Zhang, X., Chen, W."Role of oxidative stress in Alzheimer's disease (Review)". Biomedical Reports 4, no. 5 (2016): 519-522.