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International Journal of Alzheimer’s Disease
Volume 2013 (2013), Article ID 414817, 15 pages
http://dx.doi.org/10.1155/2013/414817
Research Article

Role of Copper and Cholesterol Association in the Neurodegenerative Process

1INIBIOLP (Instituto de Investigaciones Bioquímicas de La Plata), CCT La Plata, CONICET-UNLP, Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120 (1900) La Plata, Argentina
2CIC (Centro de Investigaciones Cardiovasculares), CCT La Plata, CONICET-UNLP, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, 60 y 120 (1900) La Plata, Argentina

Received 7 July 2013; Revised 5 September 2013; Accepted 5 September 2013

Academic Editor: Rosanna Squitti

Copyright © 2013 Nathalie Arnal et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. L. E. Hebert, P. A. Scherr, J. L. Bienias, D. A. Bennett, and D. A. Evans, “Alzheimer disease in the US population: prevalence estimates using the 2000 census,” Archives of Neurology, vol. 60, no. 8, pp. 1119–1122, 2003. View at Publisher · View at Google Scholar · View at Scopus
  2. P. M. Bagnati, R. F. Allegri, J. Kremer, and F. E. Taragano, Enfermedad de Alzheimer y Otras Demencias, Ed. Polemos, 2010.
  3. G. J. Brewer, “Issues raised involving the copper hypotheses in the causation of Alzheimer's disease,” International Journal of Alzheimer's Disease, vol. 2011, Article ID 537528, 11 pages, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. H. D. Foster, “Why the preeminent risk factor in sporadic Alzheimer's disease cannot be genetic,” Medical Hypotheses, vol. 59, no. 1, pp. 57–61, 2002. View at Publisher · View at Google Scholar · View at Scopus
  5. C. Salustri, G. Barbati, R. Ghidoni et al., “Is cognitive function linked to serum free copper levels? A cohort study in a normal population,” Clinical Neurophysiology, vol. 121, no. 4, pp. 502–507, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. G. J. Brewer, “Copper toxicity in Alzheimer's disease: cognitive loss from ingestion of inorganic copper,” Journal of Trace Elements in Medicine and Biology, vol. 26, no. 2-3, pp. 89–92, 2012. View at Publisher · View at Google Scholar
  7. R. Squitti, R. Ghidoni, F. Scrascia et al., “Free copper distinguishes mild cognitive impairment subjects from healthy elderly individuals,” Journal of Alzheimer's Disease, vol. 23, no. 2, pp. 239–248, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. R. Squitti, P. Pasqualetti, G. dal Forno et al., “Excess of serum copper not related to ceruloplasmin in Alzheimer disease,” Neurology, vol. 64, no. 6, pp. 1040–1046, 2005. View at Google Scholar · View at Scopus
  9. R. Squitti, G. Barbati, L. Rossi et al., “Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF β-amyloid, and h-tau,” Neurology, vol. 67, no. 1, pp. 76–82, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. R. Squitti, F. Bressi, P. Pasqualetti et al., “Longitudinal prognostic value of serum “free” copper in patients with Alzheimer disease,” Neurology, vol. 72, no. 1, pp. 50–55, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. N. Arnal, D. O. Cristalli, M. J. T. de Alaniz, and C. A. Marra, “Clinical utility of copper, ceruloplasmin, and metallothionein plasma determinations in human neurodegenerative patients and their first-degree relatives,” Brain Research, vol. 1319, pp. 118–130, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. D. L. Sparks and B. G. Schreurs, “Trace amounts of copper in water induce β-amyloid plaques and learning deficits in a rabbit model of Alzheimer's disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 19, pp. 11065–11069, 2003. View at Publisher · View at Google Scholar · View at Scopus
  13. J. Lu, Y.-L. Zheng, D.-M. Wu, D.-X. Sun, Q. Shan, and S.-H. Fan, “Trace amounts of copper induce neurotoxicity in the cholesterol-fed mice through apoptosis,” FEBS Letters, vol. 580, no. 28-29, pp. 6730–6740, 2006. View at Publisher · View at Google Scholar · View at Scopus
  14. J. Lu, D.-M. Wu, Y.-L. Zheng et al., “Trace amounts of copper exacerbate beta amyloid-induced neurotoxicity in the cholesterol-fed mice through TNF-mediated inflammatory pathway,” Brain, Behavior, and Immunity, vol. 23, no. 2, pp. 193–203, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. P. S. Donnelly, Z. Xiao, and A. G. Wedd, “Copper and Alzheimer's disease,” Current Opinion in Chemical Biology, vol. 11, pp. 128–133, 2007. View at Google Scholar
  16. K. A. Cockell, J. Bertinato, and M. R. L'Abbé, “Regulatory frameworks for copper considering chronic exposures of the population,” American Journal of Clinical Nutrition, vol. 88, no. 3, pp. 863S–866S, 2008. View at Google Scholar · View at Scopus
  17. N. Arnal, M. J. T. de Alaniz, and C. A. Marra, “Alterations in copper homeostasis and oxidative stress biomarkers in women using the intrauterine device TCu380A,” Toxicology Letters, vol. 192, no. 3, pp. 373–378, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. N. Arnal, M. Astiz, M. J. T. de Alaniz, and C. A. Marra, “Clinical parameters and biomarkers of oxidative stress in agricultural workers who applied copper-based pesticides,” Ecotoxicology and Environmental Safety, vol. 74, no. 6, pp. 1779–1786, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. D. de la Cruz, A. Cruz, M. Arteaga, L. Castillo, and H. Tovalin, “Blood copper levels in Mexican users of the T380A IUD,” Contraception, vol. 72, no. 2, pp. 122–125, 2005. View at Publisher · View at Google Scholar · View at Scopus
  20. W. B. Grant, “Dietary links to Alzheimer’s disease,” Alzheimer's Disease Review, vol. 2, pp. 42–55, 1997. View at Google Scholar
  21. M. A. Pappolla, M. A. Smith, T. Bryant-Thomas et al., “Cholesterol, oxidative stress, and Alzheimer's disease: expanding the horizons of pathogenesis,” Free Radical Biology & Medicine, vol. 33, no. 2, pp. 173–181, 2002. View at Publisher · View at Google Scholar · View at Scopus
  22. G. Di Paolo and T.-W. Kim, “Linking lipids to Alzheimer's disease: cholesterol and beyond,” Nature Reviews Neuroscience, vol. 12, no. 5, pp. 284–296, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. M. Stefani and G. Liguri, “Colesterol in Alzheimer’s disease: unresolved questions,” Current Alzheimer Research, vol. 6, pp. 1–17, 2009. View at Google Scholar
  24. B. Schreurs, “The effects of cholesterol on learning and memory,” Neuroscience & Biobehavioral Reviews, vol. 34, no. 8, pp. 1366–1379, 2010. View at Publisher · View at Google Scholar
  25. M. C. Morris, D. A. Evans, C. C. Tangney et al., “Dietary copper and high saturated and trans fat intakes associated with cognitive decline,” Archives of Neurology, vol. 63, no. 8, pp. 1085–1088, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. P. G. Reeves, F. H. Nielsen, and G. C. Fahey Jr., “AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet,” Journal of Nutrition, vol. 123, no. 11, pp. 1939–1951, 1993. View at Google Scholar · View at Scopus
  27. National Institute of Health, Guide for the Care and Use of Laboratory Animals, NIH Publication no. 85-23, National Research Council, Bethesda, Md, USA, 1985.
  28. K. A. Cockell, A. T. L. Wotherspoon, B. Belonje et al., “Limited effects of combined dietary copper deficiency/iron overload on oxidative stress parameters in rat liver and plasma,” Journal of Nutritional Biochemistry, vol. 16, no. 12, pp. 750–756, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. C. D. Davis and S. Newman, “Inadequate dietary copper increases tumorigenesis in the Min mouse,” Cancer Letters, vol. 159, no. 1, pp. 57–62, 2000. View at Publisher · View at Google Scholar · View at Scopus
  30. G. Paxinos and C. Watson, The Rat Brain in Stereotaxic Coordinates, Academic Press, Boston, Mass, USA, 4th edition, 1998.
  31. M. Berkovitch, E. Heyman, R. Afriat et al., “Copper and zinc blood levels among children with nonorganic failure to thrive,” Clinical Nutrition, vol. 22, no. 2, pp. 183–186, 2003. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Terrés-Martos, M. Navarro-Alarcón, F. Martín-Lagos, H. López-G de la Serrana, and M. C. López-Martínez, “Determination of copper levels in serum of healthy subjects by atomic absorption spectrometry,” Science of The Total Environment, vol. 198, no. 1, pp. 97–103, 1997. View at Publisher · View at Google Scholar
  33. S. Martínez-Subiela, F. Tecles, and J. J. Ceron, “Comparison of two automated spectrophotometric methods for ceruloplasmin measurement in pigs,” Research in Veterinary Science, vol. 83, no. 1, pp. 12–19, 2007. View at Publisher · View at Google Scholar · View at Scopus
  34. P. J. Twomey, A. S. Wierzbicki, I. M. Hose, A. Viljoen, and T. M. Reynolds, “Percentage non-ceruloplasmin bound copper,” Clinical Biochemistry, vol. 40, no. 9-10, pp. 749–750, 2007. View at Publisher · View at Google Scholar
  35. J. Folch, M. Lees, and G. H. Sloane Stanley, “A simple method for the isolation and purification of total lipides from animal tissues,” The Journal of Biological Chemistry, vol. 226, no. 1, pp. 497–509, 1957. View at Google Scholar · View at Scopus
  36. C. A. Marra and M. J. T. De Alaniz, “Neutral and polar lipid metabolism in liver microsomes of growing rats fed a calcium-deficient diet,” Biochimica et Biophysica Acta, vol. 1686, no. 3, pp. 220–237, 2005. View at Publisher · View at Google Scholar · View at Scopus
  37. K. Yagi, “A simple fluorometric assay for lipoperoxide in blood plasma,” Biochemical Medicine, vol. 15, no. 2, pp. 212–216, 1976. View at Google Scholar · View at Scopus
  38. K. M. Miranda, M. G. Espey, and D. A. Wink, “A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite,” Nitric Oxide, vol. 5, no. 1, pp. 62–71, 2001. View at Publisher · View at Google Scholar · View at Scopus
  39. A. Z. Reznick and L. Packer, “Oxidative damage to proteins: spectrophotometric method for carbonyl assay,” Methods in Enzymology, vol. 233, pp. 357–363, 1994. View at Publisher · View at Google Scholar · View at Scopus
  40. M. E. Anderson and A. Meister, “Enzymic assay of GSSG plus GSH,” Methods in Enzymology, vol. 105, pp. 448–450, 1984. View at Google Scholar
  41. J. L. Buttriss and A. T. Diplock, “High-performance liquid chromatography methods for vitamin E in tissues,” Methods in Enzymology, vol. 105, pp. 131–138, 1984. View at Google Scholar · View at Scopus
  42. M. Bagnati, R. Bordone, C. Perugini, C. Cau, E. Albano, and G. Bellomo, “Cu(I) availability paradoxically antagonizes antioxidant consumption and lipid peroxidation during the initiation phase of copper-induced LDL oxidation,” Biochemical and Biophysical Research Communications, vol. 253, no. 2, pp. 235–240, 1998. View at Publisher · View at Google Scholar · View at Scopus
  43. I. Carlberg and B. Mannervik, “Glutathione reductase,” Methods in Enzymology, vol. 113, pp. 484–490, 1985. View at Google Scholar · View at Scopus
  44. N. Botha, M. M. Gehringer, T. G. Downing, M. van de Venter, and E. G. Shephard, “The role of microcystin-LR in the induction of apoptosis and oxidative stress in CaCo2 cells,” Toxicon, vol. 43, no. 1, pp. 85–92, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. M. Zana, Z. Janka, and J. Kálmán, “Oxidative stress: a bridge between Down's syndrome and Alzheimer's disease,” Neurobiology of Aging, vol. 28, no. 5, pp. 648–676, 2007. View at Google Scholar
  46. D. Praticò, “Oxidative stress hypothesis in Alzheimer's disease: a reappraisal,” Trends in Pharmacological Sciences, vol. 29, no. 12, pp. 609–615, 2008. View at Publisher · View at Google Scholar
  47. F. Song, A. Poljak, G. A. Smythe, and P. Sachdev, “Plasma biomarkers for mild cognitive impairment and Alzheimer's disease,” Brain Research Reviews, vol. 61, no. 2, pp. 69–80, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. F. Mangialasche, M. C. Polidori, R. Monastero et al., “Biomarkers of oxidative and nitrosative damage in Alzheimer's disease and mild cognitive impairment,” Ageing Research Reviews, vol. 8, no. 4, pp. 285–305, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. A. Skoumalová and J. Hort, “Blood markers of oxidative stress in Alzheimer's disease,” Journal of Cellular and Molecular Medicine, vol. 16, pp. 2291–2300, 2012. View at Google Scholar
  50. E. A. Kosenko, G. Aliev, L. A. Tikhonova, Y. Li, A. C. Poghosyan, and Y. G. Kaminsky, “Antioxidant status and energy state of erythrocytes in Alzheimer dementia: probing for markers,” CNS & Neurological Disorders—Drug Targets, vol. 11, no. 7, pp. 926–932, 2012. View at Publisher · View at Google Scholar
  51. N. López, C. Tormo, I. De Blas, I. Llinares, and J. Alom, “Oxidative stress in Alzheimer's disease and mild cognitive impairment with high sensitivity and specificity,” Journal of Alzheimer's Disease, vol. 33, pp. 823–829, 2013. View at Google Scholar
  52. M. C. Badía, E. Giraldo, F. Dasí et al., “Reductive stress in young healthy individuals at risk of Alzheimer disease,” Free Radical Biology & Medicine, vol. 63, pp. 274–279, 2013. View at Publisher · View at Google Scholar
  53. A. Campbell, M. A. Smith, L. M. Sayre, S. C. Bondy, and G. Perry, “Mechanisms by which metals promote events connected to neurodegenerative diseases,” Brain Research Bulletin, vol. 55, no. 2, pp. 125–132, 2001. View at Publisher · View at Google Scholar · View at Scopus
  54. L. Rossi, R. Squitti, L. Calabrese, G. Rotilio, and P. M. Rossini, “Alteration of peripheral markers of copper homeostasis in Alzheimer's disease patients: implications in aetiology and therapy,” Journal of Nutrition, Health and Aging, vol. 11, no. 5, pp. 408–417, 2007. View at Google Scholar · View at Scopus
  55. J. H. Viles, “Metal ions and amyloid fiber formation in neurodegenerative diseases. Copper, zinc and iron in Alzheimer's, Parkinson's and prion diseases,” Coordination Chemistry Reviews, vol. 256, no. 19-20, pp. 2271–2284, 2012. View at Publisher · View at Google Scholar
  56. R. Squitti, “Metals in alzheimer's disease: a systemic perspective,” Frontiers in Bioscience, vol. 17, no. 2, pp. 451–472, 2012. View at Publisher · View at Google Scholar · View at Scopus
  57. S. Kojima, O. Matsuki, T. Nomura et al., “Localization of glutathione and induction of glutathione synthesis- related proteins in mouse brain by low doses of γ-rays,” Brain Research, vol. 808, no. 2, pp. 262–269, 1998. View at Publisher · View at Google Scholar · View at Scopus
  58. Y. Sharma, S. Bashir, M. Irshad, T. C. Nag, and T. D. Dogra, “Dimethoate-induced effects on antioxidant status of liver and brain of rats following subchronic exposure,” Toxicology, vol. 215, no. 3, pp. 173–181, 2005. View at Publisher · View at Google Scholar · View at Scopus
  59. R. Dringen, “Metabolism and functions of glutathione in brain,” Progress in Neurobiology, vol. 62, no. 6, pp. 649–671, 2000. View at Publisher · View at Google Scholar · View at Scopus
  60. R. Dringen, “Oxidative and antioxidative potential of brain microglial cells,” Antioxidants and Redox Signaling, vol. 7, no. 9-10, pp. 1223–1233, 2005. View at Publisher · View at Google Scholar · View at Scopus
  61. V. Pallottini, C. Martini, A. M. Bassi, P. Romano, G. Nanni, and A. Trentalance, “Rat HMGCoA reductase activation in thioacetamide-induced liver injury is related to an increased reactive oxygen species content,” Journal of Hepatology, vol. 44, no. 2, pp. 368–374, 2006. View at Publisher · View at Google Scholar · View at Scopus
  62. F. W. Pfrieger and N. Ungerer, “Cholesterol metabolism in neurons and astrocytes,” Progress in Lipid Research, vol. 50, no. 4, pp. 357–371, 2011. View at Publisher · View at Google Scholar · View at Scopus
  63. V. Leoni and C. Caccia, “Oxysterols as biomarkers in neurodegenerative diseases,” Chemistry and Physics of Lipids, vol. 164, no. 6, pp. 515–524, 2011. View at Publisher · View at Google Scholar · View at Scopus
  64. M. Stefani and G. Liguri, “Cholesterol in Alzheimer's disease: unresolved questions,” Current Alzheimer Research, vol. 6, no. 1, pp. 15–29, 2009. View at Publisher · View at Google Scholar · View at Scopus
  65. S. Takeda, N. Sato, K. Ikimura, H. Nishino, H. Rakugi, and R. Morishita, “Increased blood-grain barrier vulnerability to systemic inflammation in an Alzheimer disease mouse model,” Neurobiology of Aging, vol. 34, no. 8, pp. 2064–2070, 2013. View at Publisher · View at Google Scholar
  66. J. Wang, K. Ohno-Matsui, and I. Morita, “Cholesterol enhances amyloid β deposition in mouse retina by modulating the activities of Aβ-regulating enzymes in retinal pigment epithelial cells,” Biochemical and Biophysical Research Communications, vol. 424, no. 4, pp. 704–709, 2012. View at Publisher · View at Google Scholar
  67. J. L. Galbete, T. Rodriguez-Martin, E. Peressini, P. Modena, R. Bianchi, and G. Forloni, “Cholesterol decreases secretion of the secreted form of amyloid precursor protein by interfering with glycosylation in the protein secretory pathway,” Biochemical Journal, vol. 348, no. 2, pp. 307–313, 2000. View at Publisher · View at Google Scholar · View at Scopus
  68. P. A. Svensson, M. C. Englund, E. Markström et al., “Copper induces the expression of cholesterogenic genes in human macrophages,” Atherosclerosis, vol. 169, no. 1, pp. 71–76, 2003. View at Publisher · View at Google Scholar
  69. D. L. Sparks, C. Ziolkowski, T. Lawmaster, and T. Martin, “Influence of water quality on cholesterol-induced tau pathology: preliminary data,” International Journal of Alzheimer's Disease, vol. 2011, Article ID 987023, 7 pages, 2011. View at Publisher · View at Google Scholar
  70. C. R. Jack Jr., D. S. Knopman, W. J. Jagust et al., “Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade,” The Lancet Neurology, vol. 9, no. 1, pp. 119–128, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. C. R. Jack Jr., V. J. Lowe, S. D. Weigand et al., “Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer's disease: implications for sequence of pathological events in Alzheimer's disease,” Brain, vol. 132, part 5, pp. 1355–1365, 2009. View at Publisher · View at Google Scholar
  72. H. Zetterberg, k. Blennow, and E. Hanse, “Amyloid beta and APP as biomarkers for Alzheimer's disease,” Experimental Gerontology, vol. 45, no. 1, pp. 23–29, 2010. View at Publisher · View at Google Scholar
  73. A. Tamaoka, T. Fukushima, N. Sawamura et al., “Amyloid β protein in plasma from patients with sporadic Alzheimer' s disease,” Journal of the Neurological Sciences, vol. 141, no. 1-2, pp. 65–68, 1996. View at Publisher · View at Google Scholar · View at Scopus
  74. P. Lewczuk, J. Kornhuber, E. Vanmechelen et al., “Amyloid β peptides in plasma in early diagnosis of Alzheimer's disease: a multicenter study with multiplexing,” Experimental Neurology, vol. 223, no. 2, pp. 366–370, 2010. View at Publisher · View at Google Scholar · View at Scopus
  75. P. J. Crouch, S. M. Harding, A. R. White, J. Camakaris, A. I. Bush, and C. L. Masters, “Mechanisms of A beta mediated neurodegeneration in Alzheimer's disease,” The International Journal of Biochemistry & Cell Biology, vol. 40, no. 2, pp. 181–198, 2008. View at Publisher · View at Google Scholar
  76. E. Tamagno, G. Robino, A. Obbili et al., “H2O2 and 4-hydroxynonenal mediate amyloid β-induced neuronal apoptosis by activating JNKs and p38MAPK,” Experimental Neurology, vol. 180, no. 2, pp. 144–155, 2003. View at Publisher · View at Google Scholar · View at Scopus
  77. B. R. Ahn, H. E. Moon, H. R. Kim, H. A. Jung, and J. S. Choi, “Neuroprotective effect of edible brown alga Eisenia bicyclis on amyloid betapeptide-induced toxicity in PC12 cells,” Archives of Pharmacal Research, vol. 35, no. 11, pp. 1989–1998, 2012. View at Google Scholar
  78. T. Luo, W. Jiang, Y. Kong et al., “The protective effects of jatrorrhizine on β-amyloid (25-35)-induced neurotoxicity in rat cortical neurons,” CNS & Neurological Disorders Drug Targets, vol. 11, no. 8, pp. 1030–1037, 2012. View at Google Scholar
  79. V. V. dos Santos, D. B. Santos, G. Lach et al., “Neuropeptide Y (NPY) prevents depressive-like behavior, spatial memory deficits and oxidative stress following amyloid-β (Aβ1-40) administration in mice,” Behavioural Brain Research, vol. 244, pp. 107–115, 2013. View at Publisher · View at Google Scholar
  80. T. Harkany, I. Abrahám, C. Kónya et al., “Mechanisms of beta-amyloid neurotoxicity: perspectives of pharmacotherapy,” Reviews in the Neurosciences, vol. 11, no. 4, pp. 329–382, 2000. View at Google Scholar
  81. C.-A. Yang, Y.-H. Chen, S.-C. Ke et al., “Correlation of copper interaction, copper-driven aggregation, and copper-driven H2O2 formation with Aβ40 conformation,” International Journal of Alzheimer's Disease, vol. 2011, Article ID 607861, 7 pages, 2011. View at Publisher · View at Google Scholar · View at Scopus
  82. D. Paola, C. Domenicotti, M. Nitti et al., “Oxidative stress induces increase in intracellular amyloid β-protein production and selective activation of βI and βII PKCs in NT2 cells,” Biochemical and Biophysical Research Communications, vol. 268, no. 2, pp. 642–646, 2000. View at Publisher · View at Google Scholar · View at Scopus
  83. E. Tamagno, M. Parola, P. Bardini et al., “β-site APP cleaving enzyme up-regulation induced by 4-hydroxynonenal is mediated by stress-activated protein kinases pathways,” Journal of Neurochemistry, vol. 92, no. 3, pp. 628–636, 2005. View at Publisher · View at Google Scholar · View at Scopus
  84. C.-J. Lin, H.-C. Huang, and Z.-F. Jiang, “Cu(II) interaction with amyloid-β peptide: a review of neuroactive mechanisms in AD brains,” Brain Research Bulletin, vol. 82, no. 5-6, pp. 235–242, 2010. View at Publisher · View at Google Scholar · View at Scopus
  85. D. Galasko and T. J. Montine, “Biomarkers of oxidative damage and inflammation in Alzheimer’s disease,” Biomarkers in Medicine, vol. 4, no. 1, pp. 27–36, 2010. View at Publisher · View at Google Scholar · View at Scopus
  86. N. Arnal, M. J. de Alaniz, and C. A. Marra, “Cytotoxic effects of copper overload on human-derived lung and liver cells in culture,” Biochimica et Biophysica Acta, vol. 1820, no. 7, pp. 931–939, 2012. View at Publisher · View at Google Scholar
  87. K.-I. Saito, J. S. Elce, J. E. Hamos, and R. A. Nixon, “Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 7, pp. 2628–2632, 1993. View at Google Scholar · View at Scopus
  88. R. A. Nixon, “The calpains in aging and aging-related diseases,” Ageing Research Reviews, vol. 2, no. 4, pp. 407–418, 2003. View at Publisher · View at Google Scholar · View at Scopus
  89. F. Trinchese, M. Fa', S. Liu et al., “Inhibition of calpains improves memory and synaptic transmission in a mouse model of Alzheimer disease,” The Journal of Clinical Investigation, vol. 118, no. 8, pp. 2796–2807, 2008. View at Publisher · View at Google Scholar · View at Scopus
  90. S. W. Scheff and D. A. Price, “Synaptic pathology in Alzheimer's disease: a review of ultrastructural studies,” Neurobiology of Aging, vol. 24, no. 8, pp. 1029–1046, 2003. View at Publisher · View at Google Scholar · View at Scopus
  91. P. C. Amadoruge and K. J. Barnham, “Alzheimer's disease and metals: a review of the involvement of cellular membrane receptors in metallosignalling,” International Journal of Alzheimer's Disease, vol. 2011, Article ID 542043, 9 pages, 2011. View at Publisher · View at Google Scholar · View at Scopus
  92. M. Costa, O. Cantoni, M. de Mars, and D. E. Swartzendruber, “Toxic metals produce an S-phase-specific cell cycle block,” Research Communications in Chemical Pathology and Pharmacology, vol. 38, no. 3, pp. 405–419, 1982. View at Google Scholar · View at Scopus
  93. R. Newhook, H. Hirtle, K. Byrne, and M. E. Meek, “Releases from copper smelters and refineries and zinc plants in Canada: human health exposure and risk characterization,” Science of the Total Environment, vol. 301, no. 1–3, pp. 23–41, 2003. View at Publisher · View at Google Scholar · View at Scopus
  94. N. Arnal, M. J. de Alaniz, and C. A. Marra, “Involvement of copper overload in human diseases,” in Metals in Biology Systems, pp. 1–28, Research Signpost, 2010. View at Google Scholar
  95. F. Y. Leung, “Trace elements in parenteral micronutrition,” Clinical Biochemistry, vol. 28, no. 6, pp. 561–566, 1995. View at Publisher · View at Google Scholar · View at Scopus
  96. J. A. Cuthbert, “Wilson's disease: a new gene and an animal model for an old disease,” Journal of Investigative Medicine, vol. 43, no. 4, pp. 323–336, 1995. View at Google Scholar · View at Scopus
  97. I.-L. Notkola, R. Sulkava, J. Pekkanen et al., “Serum total cholesterol, apolipoprotein E ε4 allele, and Alzheimer's disease,” Neuroepidemiology, vol. 17, no. 1, pp. 14–20, 1998. View at Publisher · View at Google Scholar · View at Scopus
  98. R. Squitti, D. L. Sparks, T. U. Hoogenraad, and G. J. Brewer, “Copper status in Alzheimer's disease and other neurodegenerative disorders: genetics, mechanisms, neurophysiology, and therapies,” International Journal of Alzheimer's Disease, vol. 2011, Article ID 903940, 2 pages, 2011. View at Publisher · View at Google Scholar · View at Scopus
  99. R. Squitti, “Copper dysfunction in Alzheimer's disease: from meta-anlysis of biochemical studies to new insight into genetics,” Journal of Trace Elements in Medicine and Biology, vol. 26, no. 2-3, pp. 93–96, 2012. View at Publisher · View at Google Scholar