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Biochemistry (Moscow)

, Volume 79, Issue 5, pp 391–396 | Cite as

Role of zinc and copper ions in the pathogenetic mechanisms of Alzheimer’s and Parkinson’s diseases

  • E. V. StelmashookEmail author
  • N. K. Isaev
  • E. E. Genrikhs
  • G. A. Amelkina
  • L. G. Khaspekov
  • V. G. Skrebitsky
  • S. N. Illarioshkin
Review

Abstract

Disbalance of zinc (Zn2+) and copper (Cu2+) ions in the central nervous system is involved in the pathogenesis of numerous neurodegenerative disorders such as multisystem atrophy, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, Wilson-Konovalov disease, Alzheimer’s disease, and Parkinson’s disease. Among these, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most frequent age-related neurodegenerative pathologies with disorders in Zn2+ and Cu2+ homeostasis playing a pivotal role in the mechanisms of pathogenesis. In this review we generalized and systematized current literature data concerning this problem. The interactions of Zn2+ and Cu2+ with amyloid precursor protein (APP), β-amyloid (Abeta), tau-protein, metallothioneins, and GSK3β are considered, as well as the role of these interactions in the generation of free radicals in AD and PD. Analysis of the literature suggests that the main factors of AD and PD pathogenesis (oxidative stress, structural disorders and aggregation of proteins, mitochondrial dysfunction, energy deficiency) that initiate a cascade of events resulting finally in the dysfunction of neuronal networks are mediated by the disbalance of Zn2+ and Cu2+.

Key words

zinc ions copper ions Alzheimer’s disease Parkinson’s disease mitochondria-targeted antioxidants 

Abbreviations

Abeta

β-amyloid

AD

Alzheimer’s disease

APP

amyloid precursor protein

ASN

alpha-synuclein

GABA

γ-aminobutyric acid

GSK3β

glycogen synthase kinase 3β

MPP(+)

1-methyl-4-phenylpyridine

MPTP

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NMDA

N-methyl-D-aspartate

6-OHDA

6-hydroxydopamine

PD

Parkinson’s disease

ROS

reactive oxygen species

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References

  1. 1.
    Jellinger, K. A. (2013) Int. Rev. Neurobiol., 110, 1–47.PubMedCrossRefGoogle Scholar
  2. 2.
    Dunkel, P., Chai, C. L., Sperlagh, B., Huleatt, P. B., and Matyus, P. (2012) Expert. Opin. Investig. Drugs, 21, 1267–1308.PubMedCrossRefGoogle Scholar
  3. 3.
    Barnham, K. J., and Bush, A. I. (2008) Curr. Opin. Chem. Biol., 12, 222–228.PubMedCrossRefGoogle Scholar
  4. 4.
    Ward, R. J., Dexter, D. T., and Crichton, R. R. (2012) Curr. Med. Chem., 19, 2760–2772.PubMedCrossRefGoogle Scholar
  5. 5.
    Schlief, M. L., West, T., Craig, A. M., Holtzman, D. M., and Gitlin, J. D. (2006) Proc. Natl. Acad. Sci. USA, 103, 14919–14924.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Telianidis, J., Hung, Y. H., Materia, S., and Fontaine, S. L. (2013) Front Aging Neurosci., 5, 44.PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Smart, T. G., Hosie, A. M., and Miller, P. S. (2004) Neuroscientist, 10, 432–442.PubMedCrossRefGoogle Scholar
  8. 8.
    Bitanihirwe, B. K., and Cunningham, M. G. (2009) Synapse, 63, 1029–1049.PubMedCrossRefGoogle Scholar
  9. 9.
    Adlard, P. A., Parncutt, J. M., Finkelstein, D. I., and Bush, A. I. (2010) J. Neurosci., 30, 1631–1636.PubMedCrossRefGoogle Scholar
  10. 10.
    Isaev, N. K., Lozier, E. R., Novikova, S. V., Silachev, D. N., Zorov, D. B., and Stelmashook, E. V. (2012) Brain Res. Bull., 87, 80–84.PubMedCrossRefGoogle Scholar
  11. 11.
    Isaev, N. K., Stelmashook, E. V., Lukin, S. V., Freyer, D., Mergenthaler, P., and Zorov, D. B. (2010) Cell Mol. Neurobiol., 30, 877–883.PubMedCrossRefGoogle Scholar
  12. 12.
    Ayton, S., Lei, P., and Bush, A. I. (2012) Free Rad. Biol. Med., 62, 76–89.PubMedCrossRefGoogle Scholar
  13. 13.
    Mo, Z. Y., Zhu, Y. Z., Zhu, H. L., Fan, J. B., Chen, J., and Liang, Y. (2009) J. Biol. Chem., 284, 34648–34657.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Craddock, T. J., Tuszynski, J. A., Chopra, D., Casey, N., Goldstein, L. E., Hameroff, S. R., and Tanzi, R. E. (2012) PLoS One, 7, e33552.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Baum, L., Chan, I. H., Cheung, S. K., Goggins, W. B., Mok, V., Lam, L., Leung, V., Hui, E., Ng, C., Woo, J., Chiu, H. F., Zee, B. C., Cheng, W., Chan, M. H., Szeto, S., Lui, V., Tsoh, J., Bush, A. I., Lam, C. W., and Kwok, T. (2010) Biometals, 23, 173–179.PubMedCrossRefGoogle Scholar
  16. 16.
    Brewer, G. J., Kanzer, S. H., Zimmerman, E. A., Molho, E. S., Celmins, D. F., Heckman, S. M., and Dick, R. (2010) Am. J. Alzheimer’s Dis. Other Demen., 25, 572–575.CrossRefGoogle Scholar
  17. 17.
    Hozumi, I., Hasegawa, T., Honda, A., Ozawa, K., Hayashi, Y., Hashimoto, K., Yamada, M., Koumura, A., Sakurai, T., Kimura, A., Tanaka, Y., Satoh, M., and Inuzuka, T. (2011) J. Neurol. Sci., 303, 95–99.PubMedCrossRefGoogle Scholar
  18. 18.
    Loef, M., von Stillfried, N., and Walach, H. (2012) Nutr. Neurosci., 15, 2–12.PubMedCrossRefGoogle Scholar
  19. 19.
    Miller, L. M., Wang, Q., Telivala, T. P., Smith, R. J., Lanzirotti, A., and Miklossy, J. (2006) J. Struct. Biol., 155, 30–37.PubMedCrossRefGoogle Scholar
  20. 20.
    Squitti, R., Gorgone, G., Binetti, G., Ghidoni, R., Pasqualetti, P., Draicchio, F., Albini, E., Benedetti, L., Lucchini, R., and Rossini, P. M. (2007) G. Ital. Med. Lav. Ergon., 29(3 Suppl.), 294–296.PubMedGoogle Scholar
  21. 21.
    Akatsu, H., Hori, A., Yamamoto, T., Yoshida, M., Mimuro, M., Hashizume, Y., Tooyama, I., and Yezdimer, E. M. (2012) Biometals, 25, 337–350.PubMedCrossRefGoogle Scholar
  22. 22.
    Pajonk, F. G., Kessler, H., Supprian, T., Hamzei, P., Bach, D., Schweickhardt, J., Herrmann, W., Obeid, R., Simons, A., Falkai, P., Multhaup, G., and Bayer, T. A. (2005) J. Alzheimer’s Dis., 8, 23–27.Google Scholar
  23. 23.
    Damante, C. A., Osz, K., Nagy, Z., Grasso, G., Pappalardo, G., Rizzarelli, E., and Sovago, I. (2011) Inorg. Chem., 50, 5342–5350.PubMedCrossRefGoogle Scholar
  24. 24.
    Brewer, G. J. (2012) J. Trace Elem. Med. Biol., 26, 89–92.PubMedCrossRefGoogle Scholar
  25. 25.
    Hickey, J. L., Crouch, P. J., Mey, S., Caragounis, A., White, J. M., White, A. R., and Donnelly, P. S. (2011) Dalton Trans., 40, 1338–1347.PubMedCrossRefGoogle Scholar
  26. 26.
    Lovell, M. A., Xiong, S., Xie, C., Davies, P., and Markesbery, W. R. (2004) J. Alzheimer’s Dis., 6, 659–671.Google Scholar
  27. 27.
    Crouch, P. J., Hung, L. W., Adlard, P. A., Cortes, M., Lal, V., Filiz, G., Perez, K. A., Nurjono, M., Caragounis, A., Du, T., Laughton, K., Volitakis, I., Bush, A. I., Li, Q. X., Masters, C. L., Cappai, R., Cherny, R. A., Donnelly, P. S., White, A. R., and Barnham, K. J. (2009) Proc. Natl. Acad. Sci. USA, 106, 381–386.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    White, A. R., Reyes, R., Mercer, J. F., Camakaris, J., Zheng, H., Bush, A. I., Multhaup, G., Beyreuther, K., Masters, C. L., and Cappai, R. (1999) Brain Res., 842, 439–444.PubMedCrossRefGoogle Scholar
  29. 29.
    Phinney, A. L., Drisaldi, B., Schmidt, S. D., Lugowski, S., Coronado, V., Liang, Y., Horne, P., Yang, J., Sekoulidis, J., Coomaraswamy, J., Chishti, M. A., Cox, D. W., Mathews, P. M., Nixon, R. A., Carlson, G. A., St. George-Hyslop, P., and Westaway, D. (2003) Proc. Natl. Acad. Sci. USA, 100, 14193–14198.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Bayer, T. A., Schafer, S., Simons, A., Kemmling, A., Kamer, T., Tepest, R., Eckert, A., Schussel, K., Eikenberg, O., Sturchler-Pierrat, C., Abramowski, D., Staufenbiel, M., and Multhaup, G. (2003) Proc. Natl. Acad. Sci. USA, 100, 14187–14192.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    White, A. R., Multhaup, G., Maher, F., Bellingham, S., Camakaris, J., Zheng, H., Bush, A. I., Beyreuther, K., Masters, C. L., and Cappai, R. (1999) J. Neurosci., 19, 9170–9179.PubMedGoogle Scholar
  32. 32.
    Kitazawa, M., Cheng, D., and Laferla, F. M. (2009) J. Neurochem., 108, 1550–1560.PubMedCrossRefGoogle Scholar
  33. 33.
    Kessler, H., Bayer, T. A., Bach, D., Schneider-Axmann, T., Supprian, T., Herrmann, W., Haber, M., Multhaup, G., Falkai, P., and Pajonk, F. G. (2008) J. Neural Transm., 115, 1181–1187.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Telianidis, J., Hung, Y. H., Materia, S., and Fontaine, S. L. (2013) Front Aging Neurosci., 5, 44.PubMedCentralPubMedCrossRefGoogle Scholar
  35. 35.
    Capdevila, M., and Atrian, S. (2011) J. Biol. Inorg. Chem., 16, 977–989.PubMedCrossRefGoogle Scholar
  36. 36.
    Yu, W. H., Lukiw, W. J., Bergeron, C., Niznik, H. B., and Fraser, P. E. (2001) Brain Res., 894, 37–45.PubMedCrossRefGoogle Scholar
  37. 37.
    Martin, B. L., Tokheim, A. M., McCarthy, P. T., Doms, B. S., Davis, A. A., and Armitage, I. M. (2006) Mol. Cell Biochem., 283, 129–137.PubMedCrossRefGoogle Scholar
  38. 38.
    Chung, R. S., Howells, C., Eaton, E. D., Shabala, L., Zovo, K., Palumaa, P., Sillard, R., Woodhouse, A., Bennett, W. R., Ray, S., Vickers, J. C., and West, A. K. (2010) PLoS One, 5, e12030.PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Meloni, G., Faller, P., and Vasak, M. (2007) J. Biol. Chem., 282, 16068–16078.PubMedCrossRefGoogle Scholar
  40. 40.
    Ahmed, S. S., and Santosh, W. (2010) PLoS One, 5, e11252.PubMedCentralPubMedCrossRefGoogle Scholar
  41. 41.
    Tiiman, A., Palumaa, P., and Tougu, V. (2013) Neurochem. Int., 62, 367–378.PubMedCrossRefGoogle Scholar
  42. 42.
    Lee, J. Y., Son, H. J., Choi, J. H., Cho, E., Kim, J., Chung, S. J., Hwang, O., and Koh, J. Y. (2009) Brain Res., 1286, 208–214.PubMedCrossRefGoogle Scholar
  43. 43.
    Sheline, C. T., Zhu, J., Zhang, W., Shi, C., and Cai, A. L. (2013) Neurodegen. Dis., 11, 49–58.CrossRefGoogle Scholar
  44. 44.
    Tarohda, T., Ishida, Y., Kawai, K., Yamamoto, M., and Amano, R. (2005) Anal. Bioanal. Chem., 383, 224–234.PubMedCrossRefGoogle Scholar
  45. 45.
    Saini, N., and Schaffner, W. (2010) Biol. Chem., 391, 513–518.PubMedCrossRefGoogle Scholar
  46. 46.
    Chung, K. K., Zhang, Y., Lim, K. L., Tanaka, Y., Huang, H., Gao, J., Ross, C. A., Dawson, V. L., and Dawson, T. M. (2001) Nat. Med., 7, 1144–1150.PubMedCrossRefGoogle Scholar
  47. 47.
    Hristova, V. A., Beasley, S. A., Rylett, R. J., and Shaw, G. S. (2009) J. Biol. Chem., 284, 14978–14986.PubMedCentralPubMedCrossRefGoogle Scholar
  48. 48.
    Gening, L. V., Lakhin, A. V., Stelmashook, E. V., Isaev, N. K., and Tarantul, V. Z. (2013) Biochemistry (Moscow), 78, 1137–1145.CrossRefGoogle Scholar
  49. 49.
    Pall, H. S., Williams, A. C., Blake, D. R., Lunec, J., Gutteridge, J. M., Hall, M., and Taylor, A. (1987) Lancet, 2, 238–241.PubMedCrossRefGoogle Scholar
  50. 50.
    Ahmed, S. S., and Santosh, W. (2010) PLoS One, 5, e11252.PubMedCentralPubMedCrossRefGoogle Scholar
  51. 51.
    Larner, F., Sampson, B., Rehkamper, M., Weiss, D. J., Dainty, J. R., O’Riordan, S., Panetta, T., and Bain, P. (2013) Metallomics, 5, 125–132.PubMedCrossRefGoogle Scholar
  52. 52.
    Paik, S. R., Shin, H. J., Lee, J. H., Chang, C. S., and Kim, J. (1999) Biochem. J., 340, 821–828.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Rose, F., Hodak, M., and Bernholc, J. (2011) Sci. Reports, 11, 00011.Google Scholar
  54. 54.
    Wang, X., Moualla, D., Wright, J. A., and Brown, D. (2010) J. Neurochem., 113, 704–714.PubMedCrossRefGoogle Scholar
  55. 55.
    Meloni, G., and Vasak, M. (2011) Free Rad. Biol. Med., 50, 1471–1479.PubMedCrossRefGoogle Scholar
  56. 56.
    Patel, B. N., Dunn, R. J., Jeong, S. Y., Zhu, O., Julien, J.-P., and David, S. (2002) J. Neurosci., 22, 6578–6586.PubMedGoogle Scholar
  57. 57.
    Gaggelli, E., Kozlowski, H., Valensin, D., and Valensin, G. (2006) Chem. Rev., 106, 1995–2044.PubMedCrossRefGoogle Scholar
  58. 58.
    Nikam, S., Nikam, P., Ahaley, S. K., and Sontakke, A. V. (2009) Indian J. Clin. Biochem., 24, 98–101.PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Reddy, P. H., and Reddy, T. P. (2011) Curr. Alzheimer Res., 8, 393–409.PubMedCentralPubMedCrossRefGoogle Scholar
  60. 60.
    Chakrabarti, S., Munshi, S., Banerjee, K., Thakurta, I. G., Sinha, M., and Bagh, M. B. (2011) Aging Dis., 2, 242–256.PubMedCentralPubMedGoogle Scholar
  61. 61.
    Jomova, K., Vondrakova, D., Lawson, M., and Valko, M. (2010) Mol. Cell Biochem., 345, 91–104.PubMedCrossRefGoogle Scholar
  62. 62.
    Serra, J. A., Dominguez, R. O., Marschoff, E. R., Guareschi, E. M., Famulari, A. L., and Boveris, A. (2009) Neurochem. Res., 34, 2122–2132.PubMedCrossRefGoogle Scholar
  63. 63.
    Greenough, M. A., Camakaris, J., and Bush, A. I. (2013) Neurochem. Int., 62, 540–555.PubMedCrossRefGoogle Scholar
  64. 64.
    Fujimoto, Y., Maruta, S., Yoshida, A., and Fujita, T. (1984) Res. Commun. Chem. Pathol. Pharmacol., 44, 495–498.PubMedGoogle Scholar
  65. 65.
    Oteiza, P. I., Olin, K. L., Fraga, C. G., and Keen, C. L. (1995) J. Nutr., 125, 823–829.PubMedGoogle Scholar
  66. 66.
    Jimenez Del Rio, M., and Velez-Pardo, C. (2004) Arch. Med. Res., 35, 185–193.PubMedCrossRefGoogle Scholar
  67. 67.
    Leuner, K., Schutt, T., Kurz, C., Eckert, S. H., Schiller, C., Occhipinti, A., Mai, S., Jendrach, M., Eckert, G. P., Kruse, S. E., Palmiter, R. D., Brandt, U., Drose, S., Wittig, I., Willem, M., Haass, C., Reichert, A. S., and Muller, W. E. (2012) Antioxid. Redox Signal., 16, 1421–1433.PubMedCentralPubMedCrossRefGoogle Scholar
  68. 68.
    Aizenman, E., Stout, A. K., Hartnett, K. A., Dineley, K. E., McLaughlin, B., and Reynolds, I. J. (2000) J. Neurochem., 75, 1878–1888.PubMedCrossRefGoogle Scholar
  69. 69.
    Su, X. Y., Wu, W. H., Huang, Z. P., Hu, J., Lei, P., Yu, C. H., Zhao, Y. F., and Li, Y. M. (2007) Anal. Bioanal. Chem., 383, 224–234.Google Scholar
  70. 70.
    Manczak, M., Mao, P., Calkins, M. J., Cornea, A., Reddy, A. P., Murphy, M. P., Szeto, H. H., Park, B., and Reddy, P. H. (2010) J. Alzheimer’s Dis., 20, S609–S6031.Google Scholar
  71. 71.
    Ma, T., Hoeffer, C. A., Wong, H., Massaad, C. A., Zhou, P., Iadecola, C., Murphy, M. P., Pautler, R. G., and Klann, E. (2011) J. Neurosci., 31, 5589–5595.PubMedCentralPubMedCrossRefGoogle Scholar
  72. 72.
    Kapay, N. A., Popova, O. V., Isaev, N. K., Stelmashook, E. V., Kondratenko, R. V., Zorov, D. B., Skrebitsky, V. G., and Skulachev, V. P. (2012) J. Alzheimer’s Dis., 36, 377–383.Google Scholar
  73. 73.
    Kapay, N. A., Isaev, N. K., Stelmashook, E. V., Popova, O. V., Zorov, D. B., Skrebitsky, V. G., and Skulachev, V. P. (2011) Biochemistry (Moscow), 76, 1367–1370.CrossRefGoogle Scholar
  74. 74.
    Geldenhuys, W. J., and van der Schyf, C. J. (2013) Opin. Drug Discov., 8, 115–129.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2014

Authors and Affiliations

  • E. V. Stelmashook
    • 1
    Email author
  • N. K. Isaev
    • 1
    • 2
  • E. E. Genrikhs
    • 1
  • G. A. Amelkina
    • 2
  • L. G. Khaspekov
    • 1
  • V. G. Skrebitsky
    • 1
  • S. N. Illarioshkin
    • 1
  1. 1.Research Center of NeurologyRussian Academy of Medical SciencesMoscowRussia
  2. 2.Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia

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