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Iron: Effect of Overload and Deficiency

  • Robert C. Hider
  • Xiaole Kong
Chapter
First Online:
Part of the Metal Ions in Life Sciences book series (MILS, volume 13)

Abstract

Iron is a redox active metal which is abundant in the Earth’s crust. It has played a key role in the evolution of living systems and as such is an essential element in a wide range of biological phenomena, being critical for the function of an enormous array of enzymes, energy transduction mechanisms, and oxygen carriers. The redox nature of iron renders the metal toxic in excess and consequently all biological organisms carefully control iron levels. In this overview the mechanisms adopted by man to control body iron levels are described.

Low body iron levels are related to anemia which can be treated by various forms of iron fortification and supplementation. Elevated iron levels can occur systemically or locally, each giving rise to specific symptoms. Systemic iron overload results from either the hyperabsorption of iron or regular blood transfusion and can be treated by the use of a selection of iron chelating molecules. The symptoms of many forms of neurodegeneration are associated with elevated levels of iron in certain regions of the brain and iron chelation therapy is beginning to find an application in the treatment of such diseases. Iron chelators have also been widely investigated for the treatment of cancer, tuberculosis, and malaria. In these latter studies, selective removal of iron from key enzymes or iron binding proteins is sought. Sufficient selectivity between the invading organism and the host has yet to be established for such chelators to find application in the clinic.

Iron chelation for systemic iron overload and iron supplementation therapy for the treatment of various forms of anemia are now established procedures in clinical medicine. Chelation therapy may find an important role in the treatment of various neurodegenerative diseases in the near future.

Keywords

anemia iron iron chelators iron overload iron toxicity neurodegeneration 
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References

  1. 1.
    W. Schneider, Chimia 1988 , 42, 9–20.Google Scholar
  2. 2.
    R. R. Crichton, Iron Metabolism, 3rd edn., Wiley, Chichester, 2009.Google Scholar
  3. 3.
    A. K. Powell, S. L. Heath, D. Gatteschi, L. Pardi, R. Sessoli, G. Spina, F. Del Giallo, F. Pieralli, J. Am. Chem. Soc. 1995, 117, 2491–2502.Google Scholar
  4. 4.
    W. R. Harris, in “Molecular and Cellular Iron Transport”, Ed D. M. Templeton, Marcel Dekker, Inc., New York, 2002, pp. 1–40.Google Scholar
  5. 5.
    B. Halliwell, J. M. C. Gutteridge, Arch. Biochem. Biophys. 1986, 246, 501–514.PubMedGoogle Scholar
  6. 6.
    A. Ozer, R. K. Bruick, Nature Chem. Biol. 2007, 3, 144–153.Google Scholar
  7. 7.
    C. Andreini, I. Bertini, G. Cavallaro, R. J. Najmanovich, J. M. Thornton, J. Mol. Biol. 2009, 388, 256–380Google Scholar
  8. 8.
    R. C. Hider, X. Kong, Dalton Trans. 2013, 42, 3220–3229.PubMedGoogle Scholar
  9. 9.
    K. Mizutani, M. Toyoda, B. Mikami, Biochim. Biophys. Acta 2012, 1820, 203–211.PubMedGoogle Scholar
  10. 10.
    M. K. Mayle, A. M. Le, D. T. Kamei, Biochim. Biophys. Acta 2012, 1820, 264–281.PubMedCentralPubMedGoogle Scholar
  11. 11.
    W. R. Harris, Biochim. Biophys. Acta 2012, 1820, 348–361.PubMedGoogle Scholar
  12. 12.
    P. M. Harrison, P. Arosio, Biochim. Biophys. Acta 1996, 1275, 161–203.PubMedGoogle Scholar
  13. 13.
    G. A. Clegg, J. E. Fitton, P. M. Harrison, A. Treffry, Progr. Biophys. Mol. Biol. 1981, 36, 53–86.Google Scholar
  14. 14.
    S. Roberts, A. Bomford, J. Biol. Chem. 1988, 241, 3630–3637.Google Scholar
  15. 15.
    R. C. Hider, X. Kong, BioMetals 2011, 24, 1179–1187.PubMedGoogle Scholar
  16. 16.
    H. Gonshin, B. Mackenzie, U. V. Berger, Y. Gunshin1, M. F. Romero, W. F. Boron, S. Nussberger, J. L. Gollan, M. A. Hediger, Nature 1997, 388, 482–488.Google Scholar
  17. 17.
    M. Shayeghi, G. O. Latunde-Dada, J. S. Oakhill, A. H. Laftah, K. Takeuchi, N. Halliday, Y. Khan, A. Warley, F. E. McCann, R. C. Hider, D. M. Frazer, G. J. Anderson, C. D. Vulpe, R. J. Simpson, A. T. McKie, Cell 2005, 122, 789–801.PubMedGoogle Scholar
  18. 18.
    P. N. Paradkar, K. B. Zumbrennen, B. H. Paw, D. M. Ward, J. Kaplan, Mol. Cell. Biol. 2009, 29, 1007–1016.PubMedCentralPubMedGoogle Scholar
  19. 19.
    W. Chen, H. A. Dailey, B. H. Paw, Blood 2010, 116, 628–630.PubMedCentralPubMedGoogle Scholar
  20. 20.
    A.T. McKie, P. Marciani, A. Rolfs, K. Brennan, K. Wehr, D. Barrow, S. Miret, A. Bomford, T. J. Peters, F. Farzaneh, M. A. Hediger, M. W. Hentze, R. J. Simpson, Mol. Cell 2000, 5, 299–309.PubMedGoogle Scholar
  21. 21.
    A. Donovan, A. Brownlie, Y. Zhou, J. Shepard, S. J. Pratt, J. Moynihan, B. H. Paw, Anna Drejer, B. Barut, A. Zapata, T. C. Law, C. Brugnara, S. E. Lux, G. S. Pinkus, J. L. Pinkus, P. D. Kingsley, J. Palis, M. D. Fleming, N. C. Andrews, L. I. Zon, Nature 2000, 403, 776–781.Google Scholar
  22. 22.
    S. Abboud, D. J. Haile, J. Biol. Chem. 2000, 275, 19906–19912.PubMedGoogle Scholar
  23. 23.
    M. U. Muckenthaler, R. Hill in Iron Physiology and Pathophysiology in Humans, Eds J. G. Anderson, G. D. McLaren, Humana Press, New York, 2012, pp. 27–50.Google Scholar
  24. 24.
    E. W. Mullner, B. Neupert, L. C. Kuhn, Cell 1989, 58, 373–382.PubMedGoogle Scholar
  25. 25.
    K. J. Addess, J. P. Basilion, R. D. Klausner, T. A. Rouault, A. Pardi, J. Mol. Biol. 1997, 274, 72–83.PubMedGoogle Scholar
  26. 26.
    D. J. Haile, M. W. Hentze, T. A. Rouault, J. B. Harford, R. D. Klausner, Mol. Cell. Biol. 1989, 9, 5055–5061.PubMedCentralPubMedGoogle Scholar
  27. 27.
    T. Ganz, S.Vaulont, in Iron Physiology and Pathophysiology in Humans, Eds G. J. Anderson, G. D. McLaren, Humana Press, New York, 2011, pp. 173–190.Google Scholar
  28. 28.
    M. W. Hentze, M. U. Muckenthaler, B. Galy, C. Camaschella, Cell 2010, 142, 24–38.PubMedGoogle Scholar
  29. 29.
    J. J. Bullen, E. Griffiths, Iron and Infection, 2nd edn., Wiley Press, New York, 1999.Google Scholar
  30. 30.
    P. R. Dallman, M. A. Siimes, A. Stekel, Am. J. Clin. Nutr. 1980, 33, 86–118.PubMedGoogle Scholar
  31. 31.
    W. I. Leong, B. Lönnerdal in Iron Physiology and Pathophysiology in Humans, Eds G. J. Anderson, G. D. McLaren, Humana Press, New York, 2011, pp. 81–99.Google Scholar
  32. 32.
    World Health Organisation, Iron Deficiency Anaemia: Assessment, Prevention and Control. A Guide to Programme Managers, Geneva, WHO, 2001.Google Scholar
  33. 33.
    R. D. Baynes, T. H. Bothwell, Ann. Rev. Nutr. 1990, 10, 133–148.Google Scholar
  34. 34.
    F. E. Viteri, B. Torun, in Clinics in Haematology, Vol 3, Ed L. Garby, Saunders, London, 1974, pp 609–626.Google Scholar
  35. 35.
    G. W. Gardner, V. R. Edgerton, B. Senewiratne, R. J. Barnard, Y. Ohira, Am. J. Clin. Nutr. 1977, 30, 910–917.PubMedGoogle Scholar
  36. 36.
    The British Nutrition Foundation, Iron, Nutritional and Physiological Significance, Chapman and Hall, London, 1995, pp. 65–78.Google Scholar
  37. 37.
    J. D. Cook, M. B. Reddy, J. Burri, M. A. Juillerat, R. F. Hurrell, Am. J. Clin. Nutr. 1997, 65, 964–969.PubMedGoogle Scholar
  38. 38.
    P. Blaud, Rev. Med. Franç. Etranger, 1832, 45, 341–367.Google Scholar
  39. 39.
    I. H. Stockley, Stockley’s Drug Interactions, 6th edn, Pharmaceutical Press, London, 2002.Google Scholar
  40. 40.
    D. M. Reffitt, T. J. Burden, P. T. Seed, J. Wood, R. P. H. Thompson, J. Powell, Ann. Clin. Biochem. 2000, 37, 457– 466.PubMedGoogle Scholar
  41. 41.
    P. Jacobs, G. Johnson, L. Wood, J. Medicine 1984, 15, 367–377.Google Scholar
  42. 42.
    W. Schneider, W. Forth, Arzneim. Forsch. Drug Res. 1987, 37, 89–95.Google Scholar
  43. 43.
    C.N. Roy, in Iron Physiology and Pathophysiology in Humans, Eds G. J. Anderson, G. D. McLaren, Humana Press, New York, 2011, pp. 303–320.Google Scholar
  44. 44.
    C. N. Roy, D. A. Weinstein, N. C. Andrews, Pediatr. Res. 2005, 53, 507–512.Google Scholar
  45. 45.
    E. Nemeth, S. Rivera, V. Gabayan, C. Keller, S. Taudorf, B. K. Pedersen, T, Ganz, Blood 2003, 101, 2461–2463.Google Scholar
  46. 46.
    Y. S. Sohn, W. Brever, A. Munnich, Z. I. Cabantchik, Blood 2008, 111, 1690–1699.PubMedGoogle Scholar
  47. 47.
    R. W. Evans, X. Kong, R. C. Hider, Biochim. Biophys. Acta 2012, 1820, 282–290.PubMedGoogle Scholar
  48. 48.
    J. P. Kaltwasser, U. Kessler, R. Gottschalk, G. Stucki, B. Moller, J. Rheumatol. 2001, 28, 2430–2436.PubMedGoogle Scholar
  49. 49.
    L. T. Goodnough, B. Skikne, C. Brugnara, Blood 2000, 96, 823–833.PubMedGoogle Scholar
  50. 50.
    W. Y. Qunibi, Arzneimittelforschung 2010, 60, 399–412.PubMedGoogle Scholar
  51. 51.
    P. Geisser, S. Burckhurdt, Pharmaceutics 2011, 3, 12–33.PubMedCentralPubMedGoogle Scholar
  52. 52.
    L. J. Noetzli, S. M. Carson, A. S. Nord, T.D. Coates, J. C. Wood, Blood 2009, 114, 4021–4026.PubMedCentralPubMedGoogle Scholar
  53. 53.
    M. N. Silva, X. Kong, M. C. Parkin, R. Cammack, R. C Hider, Dalton Trans. 2009, 40, 8616–8625.Google Scholar
  54. 54.
    J.L. Pierre, I. Gautier-Luneau, BioMetals 2000, 13, 91–96.PubMedGoogle Scholar
  55. 55.
    R. W. Evans, R. Rafique, A. Zarea, C. Rapisarda, R. Cammack, P. J. Evans, J. B. Porter, R. C. Hider, J. Biol. Inorg. Chem. 2008, 13, 57–74.PubMedGoogle Scholar
  56. 56.
    M. N. Silva, R. C. Hider, Biochim. Biophys. Acta 2009, 1794, 1449–1458.PubMedGoogle Scholar
  57. 57.
    P. Brissot, M. Ropert, C. Le Lan, O. Loreal, Biochim. Biophys. Acta 2012, 1820, 403–410.PubMedGoogle Scholar
  58. 58.
    P. C. Adams, J. C. Barton, Lancet 2007, 370, 1855–1860.PubMedGoogle Scholar
  59. 59.
    N. C. Andrews, New Engl. J. Med. 1999, 341, 1986–1995.PubMedGoogle Scholar
  60. 60.
    A. Pietrangelo, New Engl. J. Med. 2004, 350, 2383–2397.PubMedGoogle Scholar
  61. 61.
    J. N. Feder, A. Gnirke, W. Thomas, Z. Tsuchihashi, D. A. Ruddy, A. Basava, F. Dormishian, R. Jr Domingo, M. C. Ellis, A. Fullan, L. M. Hinton, N. L. Jones, B. E. Kimmel, G. S. Kronmal, P. Lauer, V. K. Lee, D. B. Loeb, F. A. Mapa, E. McClelland, N. C. Meyer, G. A. Mintier, N. Moeller, T. Moore, E. Morikang, C. E. Prass, L. Quintana, S. M. Starnes, R. C. Schatzman, K. J. Brunke, D. T. Drayna, N. J. Risch, B. R. Bacon, R. K. Wolff, Nature 1996, 13, 399–408.Google Scholar
  62. 62.
    M. Simon, M. Bourel, R. Fauchet, B. Genetet, Gut 1976, 17, 332–334PubMedCentralPubMedGoogle Scholar
  63. 63.
    J. N. Feder, Z. Tsuchihashi, A. Irrinki, V. K. Lee, F. A. Mapa, E. Marikang, C. E. Prass, S. M. Starnes, R. K. Wolff, S. Parkkilay, W. S. Sly, R. C. Schatzman, J. Biol. Chem. 1997, 272, 14025–14028.PubMedGoogle Scholar
  64. 64.
    K. J. Allen, L. C. Gurrin, C. C. Constantine, N. J. Osborne, M. B. Delatycki, A. J. Nicol, C. E. Mcharen, M. Bahlo, A. E. Nisselle, C. D. Vulpe, G. J. Anderson, M. C. Southey, G. G. Giles, D. R. English, J. L. Hopper, J. K. Olynk, L. W. Powell, D. M. Gertig, New Engl. J. Med. 2008, 358, 221–230.PubMedGoogle Scholar
  65. 65.
    P. L. Lee, E. Beutler, Annu. Rev. Pathol. Mech. Dis. 2009, 4, 489–515.Google Scholar
  66. 66.
    T. J. Sproule, E. C. Jazwinska, R. S. Britton, B. R. Bacon, R. E. Fleming, W. S. Sly, D. C. Roopeniom, Proc. Natl. Acad. Sci. USA 2001, 98, 5170–5174.Google Scholar
  67. 67.
    C. Camaschella, A. Roetto, M. Cicilano, P. Pasquero, S. Bosio, L. Gubetta, F. Di Vito, D. Girelli, A. Totaro, M. Carella, A. Grifa, P. Gasparini, Eur. J. Hum. Genet. 1997, 5, 371–375.PubMedGoogle Scholar
  68. 68.
    G. Sebastiani, K. Pantopoulos, Metallomics 2011, 3, 971–986.PubMedGoogle Scholar
  69. 69.
    L. P. Yang, S. J. Keam, G. M. Keating, Drugs 2007, 67, 2211–2230.PubMedGoogle Scholar
  70. 70.
    S. Rivella, in Iron Physiology and Pathophysiology in Humans, Eds G. J. Anderson, G. D. McLaren, Humana Press, New York, 2012, pp. 321–341.Google Scholar
  71. 71.
    D. J. Weatherall, Ann. New York Acad. Sci. 2010, 1202, 17–23.Google Scholar
  72. 72.
    J. B. S. Haldane, Hereditas 1949, 35, 267–273.Google Scholar
  73. 73.
    D. J. Weatherall, Brit. J. Haematol. 2008, 141, 276–286.Google Scholar
  74. 74.
    H. F. Bunn, Blood 2013, 121, 20–25.PubMedGoogle Scholar
  75. 75.
    D. J. Weatherall, J. B. Clegg, Thalassaemia Syndromes, 3rd edn, Blackwell, London, 1981.Google Scholar
  76. 76.
    B. Model, M. Darlison, Bull. World Health Organ. 2008, 86, 480–487.Google Scholar
  77. 77.
    D. J. Weatherall, Brit. J. Heamatol. 2000, 321, 1117–1120.Google Scholar
  78. 78.
    G. M. Brittenham, in Hematology: Basic Principles and Practice, Eds R. Hoffman, E. Benz, S. Shattil, B. Furie, H. Cohen, Churchill Livingstone, New York, 1991, pp. 327–342.Google Scholar
  79. 79.
    R. Sephton Smith, Brit. Med. J. 1962, 1577–1580.Google Scholar
  80. 80.
    S. Dhungana, P. S. White, A. L. Crumbliss, J. Biol. Inorg. Chem. 2001, 6, 810–818.PubMedGoogle Scholar
  81. 81.
    R. D. Propper, S. B. Schurin, D. G. Nathan, New Engl. J. Med. 1976, 294, 1421–1423.PubMedGoogle Scholar
  82. 82.
    A. T. Taher, K. M. Musallam, M. D. Cappellini, D. J. Weatherall, Brit. J. Haematol. 2010, 152, 512–523.Google Scholar
  83. 83.
    S. Claster, E. P. Vichinsky, Brit. Med. J. 2003, 327, 1151–1155.PubMedCentralPubMedGoogle Scholar
  84. 84.
    M. J. Stuart, R. L. Nagel, Lancet 2004, 364, 1343–1360.PubMedGoogle Scholar
  85. 85.
    E. B. Fung, P. R. Harmatz, P. D. K. Lee, M. Milet, R. Bellevue, M. R. Jeng, K. A. Kalinyak, M. Hudes, S. Bhatia, E. P. Vinchinsky, Brit. J. Haematol. 2006, 135, 574–582.Google Scholar
  86. 86.
    N. Galtermann, E. A. Rachmilewitz, Ann. Hematol. 2011, 90, 1–10.Google Scholar
  87. 87.
    N. B. A. Roy, S. Myerson, A. H. Schuh, P. Bignell, R. Patel, J. S. Wainscoat, S. McGowan, E. Marchi, W. Atoyebi, T. Littlewood, J. Chacko, P. Vyas, S. B. Killick, Brit. J. Haematol. 2011, 154, 521–524.Google Scholar
  88. 88.
    V. Campuzano, L. Montermini, M.D. Molto, L. Pianese, M. Cossee, F. Cavalcanti, E. Monros, F. Rodius, F. Duclos, A. Monticelli, F. Zara, J. Cañizares, H. Koutnikova, S. Bidichandani, C. Gellera, A. Brice, P.Trouillas, G. De Michele, A. Filla, R. De Frutos, F. Palau, P. I. Patel, S. D. Donato, J. L. Mandel, S. Cocozza, M. Koenig, M. Pandolfo, Science 1996, 271, 1423–1427.Google Scholar
  89. 89.
    M. Babcock, D. deSilva, R. Oaks, S. Davis-Kaplan, S. Jiralerspong, L. Montermini, M. Pandolfo, J. Kaplan, Science 1997, 276, 1709–1712.PubMedGoogle Scholar
  90. 90.
    T. L. Stemmler, E. Lesuisse, D. Pain, A. Dancis, J. Biol. Chem. 2010, 285, 26737–26743.PubMedCentralPubMedGoogle Scholar
  91. 91.
    V. Campuzano, L. Montermini, M. D. Moltò, L. Pianese, M. Cossée, F. Cavalcanti, Hum. Mol. Genet. 1997, 6, 1771–1780.PubMedGoogle Scholar
  92. 92.
    D. R. Lynch, S. R. Regner, K. A. Schadt, L. S. Friedman, K. Y. Lin, M. G. St John Sutton, Expert Rev. Cardiovasc. Ther. 2012, 10, 767–777.PubMedGoogle Scholar
  93. 93.
    N. Boddaert, K. H. Le Quan Sang, A. Rötig, A. Leroy-Willig, S. Gallet, F. Brunelle, D. Sidi, J. Thalabard, A. Munnich, Z. I. Cabantchik, Blood 2007, 100, 401–408.Google Scholar
  94. 94.
    M. T. Rodríguez-Manzaneque, J. Tamarit, G. Bellí, J. Ros, E. Herrero, Mol. Biol. Cell. 2002, 13, 1109–1121.PubMedCentralPubMedGoogle Scholar
  95. 95.
    C. Camaschella, A. Campanella, L. D. Falco, L. Boschetto, R. Merlini, L. Silvestri, S. Levi, A. Iolascon, Blood 2007, 110, 1353–1358.PubMedGoogle Scholar
  96. 96.
    H. Ye, Jeong, M. C. Ghosh, G. Kovtunovych, L. Silvestri, D. Ortillo, N. Uchida, J. Tisdale, C. Camaschella, T. A. Rouault, J. Clin. Invest. 2010, 1120, 1749–1761.Google Scholar
  97. 97.
    N. C. Andrews, Nat. Rev. Genetics 2000, 1, 208–217.Google Scholar
  98. 98.
    C. C. Trenor, D. R. Campagna, V. M. Sellers, N. C. Andrews, M. D. Fleming, Blood 2000, 96, 1113–1118.PubMedGoogle Scholar
  99. 99.
    J. E. Levy, O. Jin, Y. Fujiwara, F. Kuo, N. C. Andrews, Nat. Genetics, 1999, 21, 396–399.Google Scholar
  100. 100.
    M. D. Fleming, M. A. Romano, M. A. Su, L. M. Garrick, M. D. Garrick, N. C. Andrews, Proc. Natl. Acad. Sci. USA 1998, 95, 1148–1153.PubMedCentralPubMedGoogle Scholar
  101. 101.
    S. E. Bernstein, J. Lab. Clin. Med. 1987, 110, 690–705.PubMedGoogle Scholar
  102. 102.
    E. S. Russell, E. C. McFarland, E. L. Kent, Transpl. Proc. 1970, 2, 144–151.Google Scholar
  103. 103.
    D. Sladic-Simic, P. N. Martinovich, N. Zivkovic, D. Pavic, J. Martinovic, M. Kahn, H. M. Ranney, Ann. N. Y. Acad. Sci. 1969, 165, 93–99.PubMedGoogle Scholar
  104. 104.
    C. D. Vulpe, Y. M. Kuo, T. L. Murphy, L. Cowley, C. Askwith, N. Libina, J. Gitschier, G. J. Anderson, Nat. Genet. 1999, 21, 195–199.PubMedGoogle Scholar
  105. 105.
    X. Y. Zhou, S. Tomatsu, R. E. Fleming, S. Parkkila, A. Waheed, J. Jiang, Y. Fei, E. M. Brunt, D. A. Ruddy, C. E. Prass, R. C. Schatzman, R. O’Neill, R. S. Britton, B. R. Bacon, W. S. Sly, Proc. Natl. Acad. Sci. USA 1998, 95, 2492–2497.PubMedCentralPubMedGoogle Scholar
  106. 106.
    V. Niederkofler, R. Salie, S. Arber, J. Clin. Invest. 2005, 115, 2180–2186.PubMedCentralPubMedGoogle Scholar
  107. 107.
    F. W. Huang, J. L. Pinkus, G. S. Pinkus, M. D. Fleming, N. C. Andrews, J. Clin. Invest. 2005, 115, 2187–2191.PubMedCentralPubMedGoogle Scholar
  108. 108.
    G. Nicolas, M. Bennoun, I. Devaux, C. Beaumont, B. Grandchamp, A. Kahn, Proc. Natl. Acad. Sci. USA 2001, 98, 8780–8785.PubMedCentralPubMedGoogle Scholar
  109. 109.
    R. E. Fleming, J. R. Ahmann, M. C. Migas, A. Waheed, H. P. Koeffler, H. Kawabata, R. S. Britton, B. R. Bacon, and W. S. Sly, Proc. Natl. Acad. Sci. USA 2002, 99, 10653–10658.PubMedCentralPubMedGoogle Scholar
  110. 110.
    I. E. Zohn, I. D. Domenico, A. Pollock, D. M. Ward, J. F. Goodman, X. Liang, A. J. Sanchez, L. Niswander, J. Kaplan, Blood 2007, 109, 4174–4180.PubMedCentralPubMedGoogle Scholar
  111. 111.
    R. H. Wang, C. Li, X. Xu, Y. Zheng, C. Xiao, P. Zerfas, S. Cooperman, M. Eckhaus, T. Rouault , L. Mishra, C. X. Deng, Cell Metab. 2005, 2, 399–409.PubMedGoogle Scholar
  112. 112.
    R. S. Ohgami, D. R. Campagna, E. L. Greer, B. Antiochos, A. McDonald, J. Chen, J. J. Sharp, Y. Fujiwara, J. E Barker, M. D. Fleming, Nature Genet. 2005, 37, 1264–1269.Google Scholar
  113. 113.
    M. Yamamoto, O. Nakajima, Int. J. Hematol. 2000, 72, 157–164.PubMedGoogle Scholar
  114. 114.
    S. Lyoumi, M. Abitbol, V. Andrieu, D. Henin, E. Robert, C. Schmitt, L. Gouya, H. D. Verneuil, J. C. Deybach, X. Montagutelli, C. Beaumont, H. Puy, Blood 2007, 109, 811–818.PubMedGoogle Scholar
  115. 115.
    S. Al-Mahdawi, R. M. Pinto, D. Varshney, L. Lawrence, M. B. Lowrie, S. Hughes, Z. Webster, J. Blake, J. M. Cooper, R. King, M. A. Pook, Genomics 2006, 88, 580–590.PubMedCentralPubMedGoogle Scholar
  116. 116.
    W. Chen, P. N. Paradkar, L. Li, E. L. Pierce, N. B. Langer, N. Takahashi-Makise, B. B. Hyde, O. S. Shirihai, D. M. Ward, J. Kaplan, B. H. Paw, Proc. Natl. Acad. Sci. USA 2009, 106, 16263–16268.PubMedCentralPubMedGoogle Scholar
  117. 117.
    A. Brownlie, A. Donovan, S. J. Pratt, B. H. Paw, A. C. Oates, C. Brugnara, H. E. Witkowska, S. Sassa, L. I. Zon, Nature Genet. 1998, 20, 244–250.PubMedGoogle Scholar
  118. 118.
    R. A. Wingert, J. L. Galloway, B. Barut, H. Foott, P. Fraenkel, J. L. Axe, G. J Weber, K. Dooley, A. J. Davidson, B. Schmidt, B. H. Paw, G. C. Shaw, P. Kingsley, J. Palis, H. Schubert, O. Chen, J. Kaplan, L. I. Zon, Nature 2005, 436, 1035–1039.Google Scholar
  119. 119.
    A. Donovan, A. Brownlie, M. Dorschner, Y. Zhou, S. J. Pratt, B. H. Paw, C. B. Thisse, B. Thisse, L. I. Zon, Blood 2002, 100, 4655–4659.PubMedGoogle Scholar
  120. 120.
    G. C. Shaw, J. J. Cope, L. Li, K. Corson, C. Hersey, G. E. Ackermann, B. Gwynn, A. J. Lambert, R. A. Wingert, D. Traver, N. S. Trede, B. A. Barut, Y. Zhou, E. Minet, A. Donovan, A. Brownlie, R. Balzan, M. J. Weiss, L. L. Peters, J. Kaplan, L. I. Zon, B. H. Paw, Nature 2006, 440, 96–100.PubMedGoogle Scholar
  121. 121.
    M. Petrou, B. Modell, Prenatal Diagnosis 1995, 15, 1275–1295.PubMedGoogle Scholar
  122. 122.
    Y. W. Kan, M. S. Golbus, A. M. Dozy, N. Eng. J. Med. 1976, 295, 1165–1167.Google Scholar
  123. 123.
    Y. W. Kan, A. M. Dozy, Lancet(II) 1978, 910–913.Google Scholar
  124. 124.
    A. Cao, R. Galanello, M. C. Rosatelli, Clin. Haematol. 1993, 6, 263–286.Google Scholar
  125. 125.
    C. Hershko, A. M. Konijn, G. Link, Br. J. Haematol. 1998, 101, 399–406.PubMedGoogle Scholar
  126. 126.
    P. C. Sharpe, D. R. Richardson, D. S. Kalinowski, P. V. Bernhardt, Curr. Top. Med. Chem. 2011, 11, 591–607.PubMedGoogle Scholar
  127. 127.
    Y. Ma, T. Zhou, X. Kong, R. C. Hider, Curr. Med. Chem. 2012, 19, 2816–2927.PubMedGoogle Scholar
  128. 128.
    D. C. Harris, P. Aisen, Biochim. Biophys. Acta 1973, 329, 156–158.PubMedGoogle Scholar
  129. 129.
    S. J. Rodgers, C. W. Lee, C. Y. Ng, K. N. Raymond, Inorg. Chem. 1987, 26, 1622–1625.Google Scholar
  130. 130.
    K. N. Raymond, C. J. Carrano, Acc. Chem. Res. 1979, 12, 183–190.Google Scholar
  131. 131.
    R. C. Hider, X. Kong, Nat. Prod. Reports 2010, 27, 637–657.Google Scholar
  132. 132.
    G. S. Tilbrook, R. C. Hider, in Iron Transport and Storage in Microorganisms, Plants and Animals, Vol. 35 of Metal Ions in Biological Systems, Marcel Dekker, New York, 1998, 691–730.Google Scholar
  133. 133.
    U. Fagerholm, D. Nilsson, L. Knutson, H. Lennernas, Acta Physiol. Scand. 1999, 165, 315–324.PubMedGoogle Scholar
  134. 134.
    C. A. Lipinski, F. Lombardo, B. W. Dominy, P. J. Feeney, Adv. Drug Delivery Rev. 1997, 23, 3–25.Google Scholar
  135. 135.
    R. C. Hider, Toxicol. Lett. 1995, 82–3, 961–967.Google Scholar
  136. 136.
    R. D. Abeysinghe, P. J. Robert, C. E. Cooper, K. H. MacLean, R. C. Hider, J. B. Porter, J. Biol. Chem. 1996, 271, 7965–7972.PubMedGoogle Scholar
  137. 137.
    Z. D. Liu, R. S. Kayyali, R. C. Hider, J. B. Porter, A. E. Theobald, J. Med. Chem. 2002, 45, 631–639.PubMedGoogle Scholar
  138. 138.
    L. Banci, I. Bertini, S. Ciofi-Baffoni, T. Kozyreva, K. Zovo, P. Palumaa, Nature 2010, 465, 645–648.PubMedGoogle Scholar
  139. 139.
    M. Merkofer, R. Kissner, R.C. Hider, W. H. Koppenol, Helv. Chim. Acta 2004, 87, 3021–3034.Google Scholar
  140. 140.
    M. R. Summers, A. Jacobs, D. Tudway, P. Perera, C. Ricketts, Br. J. Haematol. 1979, 42, 547–555.PubMedGoogle Scholar
  141. 141.
    M. J. Pippard, S. T. Callender, D. J. Weatherall, Clin. Sci. Mol. Med. 1978, 54, 99–106.PubMedGoogle Scholar
  142. 142.
    J. B. Porter, R. D. Abeysinghe, S. Singh, R. C. Hider, Blood, 1996, 88, 705–713.PubMedGoogle Scholar
  143. 143.
    C. Borgna-Pignatti, M. D. Cappellini, P. De Stefano, G. C. Del Vecchio, G. L. Forni, M. R. Gamberini, R. Ghilardi, A. Piga, M. A. Romeo, H. Zhao, A. Cnaan, Blood, 2006, 107,3733–3737.PubMedGoogle Scholar
  144. 144.
    M. Y. Moridani, G. S. Tilbrook, H. H. Khodr, R. C. Hider, J. Pharm. Pharmacol. 2002, 54, 349–364.PubMedGoogle Scholar
  145. 145.
    F. N. Hahn, T. J. McMurry, A. Hugi, K. N. Raymond, J. Am. Chem. Soc. 1990, 112, 1854–1860.Google Scholar
  146. 146.
    L. C. Wolfe, Sem. Hematol. 1990, 27, 117–120.Google Scholar
  147. 147.
    R. J. Bergeron, J. Wiegand, W. R. Weimar, J. R. T. Vinson, J. Bussenius, G. W. Yao, J. S. McManis, J. Med. Chem. 1999, 42, 95–108.PubMedGoogle Scholar
  148. 148.
    R. J. Bergeron, J. Wiegand, J. S. McManis, B. H. McCosar, W. R. Weimar, G. M. Brittenham, R. E. Smith, J. Med. Chem. 1999, 42, 2432–2440.PubMedGoogle Scholar
  149. 149.
    J. C. Barton, Drugs 2007, 10, 480–490.Google Scholar
  150. 150.
    R. J. Bergeron, J. Wiegand, N. Bharti, J. S. McManis, S. Singh, BioMetals 2011, 24, 239–258.PubMedCentralPubMedGoogle Scholar
  151. 151.
    H. Y. Rienhott, V. Viprakasit, L. Tay, P. Harmatz, E. Vichinsky, D. Chirnomas, J. L. Kwiatkowski, A. Tapper, W. Kramer, J. B. Porter, E. Neufeld, J. Haematol. 2011, 96, 521–525.Google Scholar
  152. 152.
    U. Heinz, K. Hegetschweiler, P. Acklin, B. Faller, R. Lattmann, H. P. Schnebli, Angew. Chem. Int. Ed. 1999, 38, 2568–2570.Google Scholar
  153. 153.
    C. Hershko, A. M. Konijn, H. P. Nick, W. Breuer, Z. I. Cabantchik, G. Link, Blood, 2001, 97, 1115–1122.PubMedGoogle Scholar
  154. 154.
    M. D. Cappellini, J. Porter, A. El-Beshlawy, C. K. Li, J. F. Seymour, M. Elalfy, N. Gattermann, S. Giraudier, J. W. Lee, L. L. Chan, K. H. Lin, C. Rose, A. Taber, S. W. Thein, V. Viprakasit, D. Habr, G. Domokos, B. Roubert, A. Kattamis, Haematologica, 2010, 95, 557–566.PubMedCentralPubMedGoogle Scholar
  155. 155.
    J. C. Wood, B. P. Kang, A. Thompson, P. Giardina, P. Harmatz, T. Glynos, C. Paley, T. D. Coates, Blood 2010, 116, 537–543.PubMedGoogle Scholar
  156. 156.
    R. Galanello, A. Piga, D. Alberti, M. C. Rouan, H. Bigler, R. Sechaud, J. Clin. Pharmacol. 2003, 43, 565–572.PubMedGoogle Scholar
  157. 157.
    C. Rafat, F. Fakhouri, J. A. Ribeil, R. Delarue, M. LeQuintrec, Amer. J. Kidney Dis. 2009, 54, 931–934.Google Scholar
  158. 158.
    R. C. Hider, G. Kontoghiorghes, J. Silver, M. A. Stockham, G. B. Patent 1984, 2118176.Google Scholar
  159. 159.
    G. J. Kontoghiorghes, M. A. Aldouri, A. V. Hoffbrand, J. Barr, B. Wonke, T. Kourouclaris, L. Sheppard, Br. Med. J. 1987, 295, 1509–1512.Google Scholar
  160. 160.
    A. Maggio, G. D. Amico, A. Morabito, M. Capra, C. Ciaccio, P. Cianciulli, F. DiGregorio, G. Garozzo, R. Malizia, C. Magnano, A. Mangiagli, G. Quarta, M. Rizzo, D. G. D`Ascola, A. Rizzo, M. Midiri, Blood Cells, Mol. Dis. 2002, 28, 196–208.Google Scholar
  161. 161.
    H. Glickstein, R. BenEl, G. Link, W. Breuer, A. M. Konijn, C. Hershko, H. Nick, Z. I. Cabantchik, Blood 2006, 108, 3195 –3203.PubMedGoogle Scholar
  162. 162.
    D. J. Pennell, V. Berdoukas, M. Karagiorga, V. Ladis, A. Piga, A. Aessopos, E. D. Gotsis, M. A. Tanner, G. C. Smith, M. A. Westwood, B. Wonke, Blood, 2006, 107, 3738 –3744.PubMedGoogle Scholar
  163. 163.
    C. Hershko, M. D. Cappellini, R. Galanello, A. Piga, G. Tognoni, G. Masera, Br. J. Haematol. 2004, 125, 545–551.PubMedGoogle Scholar
  164. 164.
    A. Pepe, A. Meloni, M. Capra, P. Cianciulli, L. Prossomariti, C. Malaventura, M. C. Putti, A. Lippi, M. A. Romeo, M. G. Bisconte, A. Filosa, V. Caruso, A. Quarta, L. Pitrolo, M. Missere, M. Midiri, G. Rossi, V. Positano, M. Lombardi, A. Maggio, Haematologica 2011, 96, 41–47.PubMedCentralPubMedGoogle Scholar
  165. 165.
    A. Cohen, R. Galanello, A. Piga, V. Sanctis, F. Tricta, Blood 2003, 102,1583–1587.PubMedGoogle Scholar
  166. 166.
    A. Ceci, P. Baiardi, M. Felisi, M. D. Cappellini, V. Carnelli, V. De Sanctis, R. Galanello, A. Maggio, G. Mosera, A. Piga, F. Schettini, I. Stefano, F. Tricta, Br. J. Haematol. 2002, 118, 330–336.PubMedGoogle Scholar
  167. 167.
    R.C. Hider, G. S. Tilbrook, Z. D. Liu, International Patent WO98/54138 (1998).Google Scholar
  168. 168.
    N. Lowther, P. Fox, B. Faller, H. Nick, Y. Jin, T. Sergejew, Y. Hirschberg, R. Oberle, H. Donnelly, Pharm. Res. 1999, 16, 434 –440.PubMedGoogle Scholar
  169. 169.
    T. Sergejew, P. Forgiarini, H. P. Schnebli, Br. J. Haematol. 2000, 110, 985–92.PubMedGoogle Scholar
  170. 170.
    Z. D. Liu, H. H. Khodr, D. Y. Liu, S. L. Lu, R. C. Hider, J. Med.Chem. 1999, 42, 4814–4823.PubMedGoogle Scholar
  171. 171.
    S. Piyamongkol, Y. M. Ma, X. L. Kong, Z. D. Liu, M. D. Aytemir, D. van der Helm, R. C. Hider, Chem. Eur. J. 2010, 16, 6374–6381.PubMedGoogle Scholar
  172. 172.
    L. D. Devanur, H. Neubert, R. C. Hider, J. Pharm. Sci. 2008, 97, 1454–1467.PubMedGoogle Scholar
  173. 173.
    L. D. Devanur, R. W. Evans, P. J. Evans, R. C. Hider, Biochem. J. 2008, 409, 439–441.PubMedGoogle Scholar
  174. 174.
    P. Evans, R. Kayyali, R. C. Hider, J. Eccleston, J. B. Porter, Transl. Res. 2010, 156, 55–61.PubMedCentralPubMedGoogle Scholar
  175. 175.
    P. J. Giardina, R. W. Grady, Semin. Hematol. 2001, 38, 360–366.PubMedGoogle Scholar
  176. 176.
    M. E. Lai, R. W. Grady, S. Vacquer, A. Pepe, M. P. Carta, P. Bina, F. Saw, P. Cianciulli, A. Maggio, R. Galanello, P. Farci, Blood Cells Mol. Dis. 2010, 45, 136–143.PubMedGoogle Scholar
  177. 177.
    V. Berdoukas, G. Chouliaras, P. Moraitis, K. Zannikos, E. Berdoussi, V. Ladis, J. Cardiovasc. Magn. Reson. 2009, 28, 11–20.Google Scholar
  178. 178.
    W. Hagar, E. Vichinsky, Brit. J. Haematol. 2008, 141, 346–356.Google Scholar
  179. 179.
    G. Lucania, A. Vitrano, A. Filosa, A. Maggio, Brit. J. Haematol. 2011, 154, 545–555.Google Scholar
  180. 180.
    E. B. Fung, P. Harmatz, M. Milet, S. K. Ballas, L. DeCastro, W. Hagar, L. Hilliard, W. Owen, N. Olivieri, K. Smith-Whitley, D. Darbari, W. Wang, E. Vichinsky, Amer. J. Hematol. 2007, 82, 255–265.Google Scholar
  181. 181.
    W. C. Wang, N. Ahmed, M. Hanna, J. Pediat. 1986, 108, 552–557.PubMedGoogle Scholar
  182. 182.
    E. Vichinsky, F. Bernaudin, G. L. Forni, R. Gardner, K. Hassell, M. M. Heeney, B. Inusa, A. Kutlar, P. Lane, L. Mathias, J. Porter, C. Tebbi, F. Wilson, L. Griffel, W. Deng, V. Giannone, T. Coates, Br. J. Haematol. 2011, 154, 387–397.PubMedCentralPubMedGoogle Scholar
  183. 183.
    M. Jaeger, C. Anul, D. Sohngen, U. Germing, W. Scheier, Drugs Today 1992, 28, 143–147.Google Scholar
  184. 184.
    G. Metzgeroth, D. Dinter, B. Schultheis, A. Dorn-Beineke, K. Lutz, O. Leismann, R. Hehlmann, J. Hastka, Ann. Hematol. 2009, 88, 301–310.PubMedGoogle Scholar
  185. 185.
    N. Galtermann, C. Finelli, M. D. Porta, P. Fenaux, A. Ganser, A. Guerci-Bresler, M. Schmid, K. Taylor, D. Vassilieff, D. Habr, G. Domokos, B. Roubert, C. Rose, Leuk. Res. 2010, 34, 1143–1150.Google Scholar
  186. 186.
    O. Kakhlon, H. Manning, W. Breuer, N. Melamed-Book, C. Lu, G. Cortopassi, A. Munnich, Z. I. Cabantchik, Blood, 2008, 112, 5219–5227.PubMedGoogle Scholar
  187. 187.
    A. Gaeta, R. C. Hider, Brit. J. Pharmacol. 2005, 146, 1041–1059.Google Scholar
  188. 188.
    K. L. Duble, M. Gerlach, V. Schunemann, A. X. Trautwein, L. Zecca, M. Gallorini, M. B. Youdim, P. Riederer and D. Ben-Shachar, Biochem. Pharmacol. 2003, 66, 489–494.Google Scholar
  189. 189.
    M. T. Núñez, P. Urrutia, N. Mena, P. Aguirre, V. Tapia, J. Salazar, BioMetals 2012, 25, 761–776.PubMedGoogle Scholar
  190. 190.
    M. T. Núñez, V. Gallardo, P. Muñoz, V. Tapia, A. Esparza, J. Salazar, H. Speisky, Free Radic. Biol. Med. 2004, 37, 953–960.PubMedGoogle Scholar
  191. 191.
    R. Lill, U. Mühlenhoff, Annu. Rev. Biochem. 2008, 77, 669–700.PubMedGoogle Scholar
  192. 192.
    A. H. Schapira, Lancet 2006, 368, 70–82.PubMedGoogle Scholar
  193. 193.
    K. Blennow, M. J. de Leon, H. Zetterberg, Lancet 2006, 368, 387–403.PubMedGoogle Scholar
  194. 194.
    R. C. Hider, Y. M. Ma, F. Molina-Holgado, A. Gaeta, S. Roy, Biochem. Soc. Trans. 2008, 36, 1304–1308.PubMedGoogle Scholar
  195. 195.
    F. Bousejra-ElGarah, C. Bijani, Y. Coppel, P. Faller and C. Hureau, Inorg. Chem. 2011, 50, 9024–9030.PubMedGoogle Scholar
  196. 196.
    M. A. Smith, P. L. R. Harris, L. M. Sayre, G. Perry, Proc. Natl. Acad. Sci. USA 1997, 94, 9866–9868.PubMedCentralPubMedGoogle Scholar
  197. 197.
    A. Kontush, Free Radic. Biol. Med. 2001, 31, 1120–1131.PubMedGoogle Scholar
  198. 198.
    J. A. Duce, A. Tsatsanis, M. A. Cater, S. A. James, E. Robb, K. Wikhe, S. L. Leong, K. Perez, T. Johanssen, M. A. Greenough, H. Cho, D. Galatis, R. D. Moir, C. L. Masters, C. McLean, R. E. Tanzi, R. Cappai, K. J. Barnham, G. D. Ciccotosto, J. T. Rogers, A. I. Bush, Cell 2010, 142, 857–867.PubMedCentralPubMedGoogle Scholar
  199. 199.
    P. Lei, S. Ayton, D. I. Finkelstein, L. Spoerri, G. D. Ciccotosto, D. K. Wright, B. X. W. Wong, P. A. Adlard, R. A. Cherny, L. Q. Lam, B. R. Roberts, I. Volitakis, G. F. Egan, C. A. McLean, R. Cappai, J. A. Duce, A. I. Bush, Nature Medicine 2012, 18, 291–296.PubMedGoogle Scholar
  200. 200.
    J. F. Schenck, E. A. Zimmerman, Z. Li, S. Adak, A. Saha, R. Tandon, K. M. Fish, C. Belden, R. W. Gillen, A. Barba, D. L. Henderson, W. Neil, T. O’Keefe, Top. Magn. Reson. Imaging 2006, 17, 41–50.PubMedGoogle Scholar
  201. 201.
    H. Akatsu, A. Hori, T. Yamamoto, M. Yoshida, M. Mimuro, Y. Hashizume, I. Tooyama, E. M. Yezdimer, BioMetals 2012, 25, 337–350.PubMedGoogle Scholar
  202. 202.
    C. E. Clarke, Brit. Med. J. 2007, 335, 441–445.PubMedCentralPubMedGoogle Scholar
  203. 203.
    Y. Agid, Lancet 1991, 337, 1321–1324.PubMedGoogle Scholar
  204. 204.
    P. Jenner, Acta Neurol. Scond. 1991, 84 Suppl. 136, 6–15.Google Scholar
  205. 205.
    P. Jenner, Lancet, 1994, 344, 796–798.PubMedGoogle Scholar
  206. 206.
    D. T. Dexter, F. R. Wells, F. Agid, Y. Agid, A. J. Lees, P. Jenner, C. D. Marsden, Lancet 1987, 330, 1219–1220.Google Scholar
  207. 207.
    E. Sofic, P. Riederer, H. Heinsen, H. Beckmann, G. P. Reynolds, G. Hebenstreit, M. B. Youdim, J. Neural. Transm. 1988, 74, 199–205.PubMedGoogle Scholar
  208. 208.
    J. Hallervorden, H. Spatz, Z. Ges. Neurol. Psychiat. 1922, 79, 254–302.Google Scholar
  209. 209.
    S. J. Hayflick, J. M. Penzien, W. Michl, U. M. Sharif, N. P. Rosman, P. G. Wheeler, Pediatric Neurology 2001, 25, 166–169.PubMedGoogle Scholar
  210. 210.
    A. Gregory, S. J. Hayflick, Folia Neuropathologica 2005, 43, 286–296.PubMedCentralPubMedGoogle Scholar
  211. 211.
    N. Gordon, Eur. J. Pediatr. Neurol. 2002, 6, 243–247.Google Scholar
  212. 212.
    T. L. Perry, M. G. Norman, V. W. Yong, S. Whiting, J. C. Crichton, S. Hansen, S. J. Kish, Ann. Neurol. 1985, 482–489.Google Scholar
  213. 213.
    R. Klein, Q. Wang, B. E. K. Klein, S. E. Moss, S. M. Meuer, Invest. Ophthalmol. Vis. Sci. 1995, 36, 182–191.PubMedGoogle Scholar
  214. 214.
    M. A. Zarbin, Arch. Ophthalmol. 2004, 122, 598–614.PubMedGoogle Scholar
  215. 215.
    P. Haly, A. H. Milam, J. L. Dunaief, Arch. Ophthalmol. 2003, 121, 1099–1105.Google Scholar
  216. 216.
    M. Hadziahmetovic, Y. Song, N. Wolkow, J. Iacovelli, L. Kautz, M. P. Roth, J. L. Dunaief, Amer. J. Pathol. 2011, 179, 335–348.Google Scholar
  217. 217.
    M. Hadziahmetovic, Y. Song, P. Ponnuru, J. Iacovelli, A. Hunter, N. Haddad, J. Beard, J. R. Connor, S. Vaulont, J. L. Dunaief, Invest. Ophthalmol. Vis. Sci. 2011, 52, 109–118.PubMedCentralPubMedGoogle Scholar
  218. 218.
    X. He, P. Hahn, J. Iacovelli, R. Wong, C. King, R. Bhisitkul, M. Massaro-Giordano, J. L. Dunaief, Prog. Retin. Eye Res. 2007, 26, 649–673.PubMedCentralPubMedGoogle Scholar
  219. 219.
    T. Zhou, Y. Ma, X. Kong, R. C. Hider, Dalton. Trans. 2012, 41, 6371–6389.PubMedGoogle Scholar
  220. 220.
    D. T. Dexter, S. A. Statton, C. Whitmore, W. Freinbichler, P. Weinberger, K. F. Tipton, L. Della Corte, R. J. Ward, R. R. Crichton, J. Neural. Transm. 2011, 118, 223–231.PubMedGoogle Scholar
  221. 221.
    M. Hadziahmetovic, Y. Song, N. Wolkow, J. Iacovelli, S. Grieco, J. Lee, A. Lyubarsky, D. Pratico, J. Connelly, M. Spino, Z. L. Harris, J. L. Dunaief, Invest. Ophthalmol. Vis. Sci. 2011, 52, 959–968.PubMedGoogle Scholar
  222. 222.
    G. L. Forni, M. Balocco, L. Cremonesi, G. Abbruzzese, R. C. Parodi, R. Marchese, Movement Disorders 2008, 23, 904–907.PubMedGoogle Scholar
  223. 223.
    G. Abbruzzese, G. Cossu, M. Balocco, R. Marchese, D. Murgia, M. Melis, R. Galanello, S. Barella, G. Matta, U. Ruffinengo, U. Bonuccelli, G. L. Forni, Haematologica 2011, 96, 1708–1711.PubMedCentralPubMedGoogle Scholar
  224. 224.
    A. I. Bush, Neurobiology of Aging 2002, 23, 1031–1038.PubMedGoogle Scholar
  225. 225.
    H. Zheng, L. M. Weiner, O. Bar-Am, S. Epsztejn, Z. I. Cabantchik, A. Warshawsky, M. B. H. Youdim, M. Fridkin, Bioorg. Med. Chem. 2005, 13, 773–783.PubMedGoogle Scholar
  226. 226.
    H. Zheng, D. Blat, M. Fridkin, J. Neural. Trans. 2006, 71, 163–172.Google Scholar
  227. 227.
    F. Molina-Holgado, A. Gaeta, P. T. Francis, R. J. Williams, R. C. Hider, J. Neurochem. 2008, 105, 2466–2476.PubMedGoogle Scholar
  228. 228.
    Y. Avramovich-Tirosh, T. Amit, O. Bar-Am, H. Zheng, M. Fridkin, M. B. Youdim, J. Neurochem. 2007, 100, 490–502.PubMedGoogle Scholar
  229. 229.
    R. A. Cherny, C. S. Atwood, M. E. Xilinas, D. N. Gray, W. D. Jones, C. A. McLean, K. J. Barnham, I. Volitakis, F. W. Fraser, Y. Kim, X. Huang, L. E. Goldstein, R. D. Moir, J. T. Lim, K. Beyreuther, H. Zheng, R. E. Tanzi, C. L. Masters, A. I. Bush, Neuron 2001, 30, 665–676.PubMedGoogle Scholar
  230. 230.
    C. W. Ritchie, A. I. Bush, A. Mackinnon, S. Macfarlane, M. Mastwyk, L. MacGregor, L. Kiers, R. Cherny, Q. X. Li, A. Tammer, D. Carrington, C. Mavros, I. Volitakis, M. Xilinas, D. Ames, S. Davis, K. Beyreuther, R. E. Tanzi, C. L. Masters, Arch. Neurol. 2005, 60, 1685–1691Google Scholar
  231. 231.
    D. Kaur, F. Yantiri, S. Rajagopalan, J. Kumar, J.Q. Mo, R. Boonplueang, V. Viswanath, R. Jacobs, L. Yang, M. F. Beal, D. DiMonte, I. Volitaskis, L. Ellerby, R. A. Cherny, A. I. Bush, J. K. Andersen, Neuron 2003, 37, 899–909.PubMedGoogle Scholar
  232. 232.
    University Hospital Lille Trial (FAIR-PARK1), http://clinicaltrials.gov/ct2/show/NCT00943748?term=FAIR-PARK-I&rank=1
  233. 233.
    Imperial College London Trial (DeferipronPD), http://clinicaltrials.gov/ct2/show/NCT01539837?term=deferiprone&rank=4
  234. 234.
    D. Song, Y. Song, M. Hadziahmetovic, Y. Zhong, J. L. Dunaief, Free Rad. Biol. Med. 2012, 53, 64–71.PubMedCentralPubMedGoogle Scholar
  235. 235.
    T.P. Kruck, J.G. Cui, M.E. Percy, W.J. Lukiw, Cell Mol. Neurobiol. 2004, 24, 443–459.PubMedGoogle Scholar
  236. 236.
    H. Schugar, D. E. Green, M. L. Bowen, L. E. Scott, T. Storr, K. Bohmerle, F. Thomas, D. D. Allen, P. R. Lockman, M. Merkel, K. H. Thompson, C. Orvig, Angew. Chem. Int. Ed. 2007, 46, 1716–1718.Google Scholar
  237. 237.
    R. C. Hider, S. Roy, Y. M. Ma, X. L. Kong, J. Preston, Metallomics 2011, 3, 239–249.PubMedGoogle Scholar
  238. 238.
    G. Liu, P. Men, W. Kudo, G. Perry, M. A. Smith, Neurosci. Lett. 2009, 455, 187–190.PubMedCentralPubMedGoogle Scholar
  239. 239.
    D. Bebbington, C. E. Dawson, S. Gaur, J. Spencer, Bioorg. Med. Chem. Lett. 2002, 12, 3297–3300.PubMedGoogle Scholar
  240. 240.
    H. Zheng, M. B. H. Youdim, M. Fridkin, J. Med. Chem. 2009, 52, 4095–4098.PubMedGoogle Scholar
  241. 241.
    L. R. Perez, K. J. Franz, Dalton Trans. 2010, 39, 2177–2187.PubMedCentralPubMedGoogle Scholar
  242. 242.
    S. V. Torti, F. M. Torti, Cancer Res. 2011, 71, 1511–1514.PubMedCentralPubMedGoogle Scholar
  243. 243.
    R. G. Stevens, B. I. Graubard, M. S. Micozzi, K. Neriishi, B. S. Blumberg, Int. J. Cancer 1994, 56, 364–369.PubMedGoogle Scholar
  244. 244.
    A. G. Smith, J. E. Francis, P. Carthew, Carcinogenesis 1990, 11, 437–444.PubMedGoogle Scholar
  245. 245.
    L. D. Miller, L. G. Coffman, J. W. Chou, M. A. Black, J. Bergh, R. D’Agostino, Jr., S. V. Torti, F. M. Torti, Cancer Res. 2011, 71, 6728–6737.PubMedCentralPubMedGoogle Scholar
  246. 246.
    S. Nekhai, V. R. Gardeuk, in Iron Physiology and Pathophysiology in Humans, Eds G. J. Anderson, G. D. McLaren, Humana Press, New York, 2012, 477–495.Google Scholar
  247. 247.
    D. B. Lovejoy, D. R. Richardson, Curr. Med. Chem. 2003, 10, 1035–1049.PubMedGoogle Scholar
  248. 248.
    H.M. Hanauske-Abel, M.-H. Park, A.-R. Hanauske, A.M. Popowicz, M. Lalande, J.E. Folk, Biochim. Biophys. Acta, 1994, 1221, 115–124.PubMedGoogle Scholar
  249. 249.
    C. Hershko, Mol. Asp. Med. 1992, 13, 113–165.Google Scholar
  250. 250.
    R. J. Bergeron, Trends Biol. Sci. 1986, 11, 133–136.Google Scholar
  251. 251.
    J. Gao, D. R. Richardson, Blood 2001, 98, 842–850.PubMedGoogle Scholar
  252. 252.
    J. Yuan, D. B. Lovejoy, D. R. Richardson, Blood 2004, 104, 1450–1458.PubMedGoogle Scholar
  253. 253.
    D. Fu, D. R. Richardson, Blood 2007, 110, 752–761.PubMedGoogle Scholar
  254. 254.
    E. D. Weinberg, Biochim. Biophys. Acta 2009, 1790, 600–605.PubMedGoogle Scholar
  255. 255.
    N. H. Carbonetti, S. Boonchai, S. H. Parry, V. Vaisanenrhen, T. K. Korhonen, P. H. William, Infection and Immunity 1986, 51, 966–968.PubMedCentralPubMedGoogle Scholar
  256. 256.
    S. Ford, R. A. Cooper, R. W. Evans, R. C. Hider, P. H. Williams, Eur. J. Biochem. 1988, 178, 477–481.PubMedGoogle Scholar
  257. 257.
    I. A. García-Montoya, T. S. Cendón, S. Arévalo-Gallegos, Q. Rascón-Cruz, Biochim. Biophys. Acta 2012, 1820, 226–236.PubMedGoogle Scholar
  258. 258.
    K. N. Raymond, E. A. Dertz, S. S. Kim, Proc. Natl. Acad. Sci. USA 2003, 100, 3584–3588.PubMedCentralPubMedGoogle Scholar
  259. 259.
    M. A. Holmes, W. Paulsene, X. Jide, C. Ratledge, R. K. Strong, Structure 2005, 13, 29–41.PubMedGoogle Scholar
  260. 260.
    J. R. Boelaert, S. J. Vandecasteele, R. Appelberg, V. R. Gordeuk, J. Infect. Dis. 2007, 195, 1745–1753.PubMedGoogle Scholar
  261. 261.
    R. C. Hider, Z. Liu, J. Pharm. Pharmacol. 1997, 49, 59–64.Google Scholar
  262. 262.
    G. F. Mabeza, Pharmacol. Ther. 1999, 81, 53–75.PubMedGoogle Scholar

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© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Institute of Pharmaceutical ScienceKing’s College LondonLondonUK

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