Role of Metals in Alzheimer Disease

Protein Misfolding Diseases: Current and Emerging Principles and Therapies

Volumn , Issue , 2010, Pages 543-558

  Roberts, Blaine R ^a,b   Bush, Ashley I ^a,b,c  

^a FLOREY INSTITUTE OF NEUROSCIENCE AND MENTAL HEALTH   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

^c MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Accessory molecules, their role and risk factors role of metals in Alzheimer disease (AD); Maldistribution of metals in AD complex with metals being pooled in plaques; role of amyloid beta in AD and A regarded as principal toxic species

Indexed keywords

EID: 84886195571     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9780470572702.ch24     Document Type: Chapter

References (86)

1. Hardy, J., Allsop, D. (1991). Amyloid deposition as the central event in the aetiology of Alzheimer's disease. Trends Pharmacol Sci, 12, 383-388.
2. Hardy, J., Selkoe, D.J. (2002). The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science, 297, 353-356.
3. Tanzi, R.E., Bertram, L. (2005). Twenty years of the Alzheimer's disease amyloid hypothesis: a genetic perspective. Cell, 120, 545-555.
4. Goate, A., Chartier-Harlin, M.C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., et al. (1991). Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature, 349, 704-706.
5. Luo, Y., Sunderland, T., Roth, G.S., Wolozin, B. (1996). Physiological levels of beta-amyloid peptide promote PC12 cell proliferation. Neurosci Lett, 217, 125-128.
6. Vigo-Pelfrey, C., Lee, D., Keim, P., Lieberburg, I., Schenk, D.B. (1993). Characterization of b-amyloid peptide from human cerebrospinal fluid. J Neurochem, 61, 1965-1968.
7. Seubert, P., Vigo-Pelfrey, C., Esch, F., Lee, M., Dovey, H., Davis, D., Sinha, S., Schlossmacher, M., Whaley, J., Swindlehurst, C., et al. (1992). Isolation and quantification of soluble Alzheimer's b-peptide from biological fluids. Nature, 359, 325-327.
8. Masters, C.L., Multhaup, G., Simms, G., Pottgiesser, J., Martins, R.N., Beyreuther, K. (1985). Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J, 4, 2757-2763.
9. Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., Johnson-Wood, K., Lee, M., Seubert, P., Davis, A., et al. (1997). Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid b-protein in both transfected cells and transgenic mice. Nat Med, 3, 67-72.
10. Jarrett, J.T., Berger, E.P., Lansbury, P.T., Jr. (1993). The carboxy terminus of the b amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease. Biochemistry, 32, 4693-4697.
11. Hilbich, C., Kisters-Woike, B., Reed, J., Masters, C.L., Beyreuther, K. (1991). Aggregation and secondary structure of synthetic amyloid b A4 peptides of Alzheimer's disease. J Mol Biol, 218, 149-163.
12. Maynard, C.J., Cappai, R., Volitakis, I., Cherny, R.A., White, A.R., Beyreuther, K., Masters, C.L., Bush, A.I., Li, Q.-X. (2002). Overexpression of Alzheimer's disease b-amyloid opposes the age-dependent elevations of brain copper and iron levels, J Biol Chem, 277, 44670-44676.
13. Melov, S., Adlard, P.A., Morten, K., Johnson, F., Golden, T.R., Hinerfeld, D., Schilling, B., Mavros, C., Masters, C.L., Volitakis, I., et al. (2007). Mitochondrial oxidative stress causes hyperphosphorylation of tau. PLoS ONE, 2, e536.
14. Yamamoto, A., Shin, R.W., Hasegawa, K., Naiki, H., Sato, H., Yoshimasu, F., Kitamoto, T. (2002). Iron(III) induces aggregation of hyperphosphorylated tau and its reduction to iron(II) reverses the aggregation: implications in the formation of neurofibrillary tangles of Alzheimer's disease. J Neurochem, 82, 1137-1147.
15. Nunomura, A., Perry, G., Pappolla, M.A., Wade, R., Hirai, K., Chiba, S., Smith, M.A. (1999). RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer's disease. J Neurosci, 19, 1959-1964.
16. Opazo, C., Huang, X., Cherny, R.A., Moir, R.D., Roher, A.E., White, A.R., Cappai, R., Masters, C.L., Tanzi, R.E., Inestrosa, N.C., Bush, A.I. (2002). Metalloenzyme-like activity of Alzheimer's disease beta-amyloid. Cu-dependent catalytic conversion of dopamine, cholesterol, and biological reducing agents to neurotoxic H(2)O(2). J Biol Chem, 277, 40302-40308.
17. Opazo, C., Luza, S., Villemagne, V.L., Volitakis, I., Rowe, C., Barnham, K.J., Strozyk, D., Masters, C.L., Cherny, R.A., Bush, A.I. (2006). Radioiodinated clioquinol as a biomarker for beta-amyloid: Zn complexes in Alzheimer's disease. Aging Cell, 5, 69-79.
18. Bush, A.I., Pettingell, W.H., Jr., Paradis, M.D., Tanzi, R.E. (1994). Modulation of Ab adhesiveness and secretase site cleavage by zinc. J Biol Chem, 269, 12152-12158.
19. Bush, A.I., Pettingell, W.H., Multhaup, G., Paradis, M.D., Vonsattel, J.P., Gusella, J.F., Beyreuther, K., Masters, C.L., Tanzi, R.E. (1994). Rapid induction of Alzheimer Ab amyloid formation by zinc. Science, 265, 1464-1467.
20. Dong, J., Atwood, C.S., Anderson, V.E., Siedlak, S.L., Smith, M.A., Perry, G., Carey, P.R. (2003). Metal binding and oxidation of amyloid-beta within isolated senile plaque cores: Raman microscopic evidence. Biochemistry, 42, 2768-2773.
21. Frederickson, C.J. (1989). Neurobiology of zinc and zinc-containing neurons. Int Rev Neurobiol, 31, 145-328.
22. Atwood, C.S., Moir, R.D., Huang, X., Bacarra, N.M.E., Scarpa, R.C., Romano, D.M., Hartshorn, M.A., Tanzi, R.E., Bush, A.I. (1998). Dramatic aggregation of Alzheimer Ab by Cu(II) is induced by conditions representing physiological acidosis. J Biol Chem, 273, 12817-12826.
23. Atwood, C.S., Scarpa, R.C., Huang, X., Moir, R.D., Jones, W.D., Fairlie, D.P., Tanzi, R.E., Bush, A.I. (2000). Characterization of copper interactions with Alzheimer Ab peptides: identification of an attomolar affinity copper binding site on Ab1-42. J Neurochem, 75, 1219-1233.
24. Bush, A.I., Pettingell, W.H., Multhaup, G., Paradis, M.D, Vonsattel, J.P., Gusella, J.F., Beyreuther, K., Masters, C.L., Tanzi, R.E. (1994). Rapid induction of Alzheimer A beta amyloid formation by zinc. Science, 265, 1464-1467.
25. Ha, C., Ryu, J., Park, C.B. (2007). Metal ions differentially influence the aggregation and deposition of Alzheimer's beta-amyloid on a solid template. Biochemistry, 46, 6118-6125.
26. Huang, X., Cuajungco, M.P., Atwood, C.S., Hartshorn, M.A., Tyndall, J., Hanson, G.R., Stokes, K.C., Leopold, M., Multhaup, G., Goldstein, L.E., et al. (1999). Cu(II) potentiation of Alzheimer Ab neurotoxicity: correlation with cell-free hydrogen peroxide production and metal reduction. J Biol Chem, 274, 37111-37116.
27. Garai, K., Sengupta, P., Sahoo, B., Maiti, S. (2006). Selective destabilization of soluble amyloid beta oligomers by divalent metal ions. Biochem Biophys Res Commun, 345, 210-215.
28. Jun, S., Saxena, S. (2007). The aggregated state of amyloid-beta peptide in vitro depends on Cu2+ ion concentration, Angew Chem Int Ed Engl, 46, 3959-3961.
29. Tougu, V., Karafin, A., Palumaa, P. (2008). Binding of zinc(II) and copper(II) to the full-length Alzheimer's amyloid-beta peptide. J Neurochem, 104, 1249-1259.
30. Stellato, F., Menestrina, G., Dalla Serra, M., Potrich, C., Tomazzolli, R., Meyer-Klaucke, W., Morante, S. (2006). Metal binding in amyloid b-peptides shows intraand inter-peptide coordination modes. Eur Biophys J, 35, 340-351.
31. Atwood, C.S., Moir, R.D., Huang, X., Scarpa, R.C., Bacarra, N.M., Romano, D.M., Hartshorn, M.A., Tanzi, R.E., Bush, A.I. (1998). Dramatic aggregation of Alzheimer Abeta by Cu(II) is induced by conditions representing physiological acidosis, J Biol Chem, 273, 12817-12826.
32. Atwood, C.S., Perry, G., Zeng, H., Kato, Y., Jones, W.D., Ling, K.Q., Huang, X., Moir, R.D., Wang, D., Sayre, L.M., et al. (2004). Copper mediates dityrosine crosslinking of Alzheimer's amyloid-beta. Biochemistry, 43, 560-568.
33. Huang, X., Atwood, C.S., Hartshorn, M.A., Multhaup, G., Goldstein, L.E., Scarpa, R.C., Cuajungco, M.P., Gray, D.N., Lim, J., Moir, R.D., et al. (1999). The Ab peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry, 38, 7609-7616.
34. Moir, R.D., Atwood, C.S., Romano, D.M., Laurans, M.H., Huang, X., Bush, A.I., Smith, J.D., Tanzi, R.E. (1999). Differential effects of apolipoprotein E isoforms on metal-induced aggregation of Ab using physiological concentrations. Biochemistry, 38, 4595-4603.
35. Dikalov, S.I., Vitek, M.P., Mason, R.P. (2004). Cupric-amyloid beta peptide complex stimulates oxidation of ascorbate and generation of hydroxyl radical, Free Radic Biol Med, 36, 340-347.
36. Nelson, T.J., Alkon, D.L. (2005). Oxidation of cholesterol by amyloid precursor protein and beta-amyloid peptide. J Biol Chem, 280, 7377-7387.
37. Tabner, B.J., Turnbull, S., El-Agnaf, O.M., Allsop, D. (2002). Formation of hydrogen peroxide and hydroxyl radicals from A(beta) and alpha-synuclein as a possible mechanism of cell death in Alzheimer's disease and Parkinson's disease. Free Radic Biol Med, 32, 1076-1083.
38. Ali, F.E., Separovic, F., Barrow, C.J., Cherny, R.A., Fraser, F., Bush, A.I., Masters, C.L., Barnham, K.J. (2005). Methionine regulates copper/hydrogen peroxide oxidation products of Abeta. J Pept Sci, 11, 353-360.
39. Ciccotosto, G.D., Tew, D., Curtain, C.C., Smith, D., Carrington, D., Masters, C.L., Bush, A.I., Cherny, R.A., Cappai, R., Barnham, K.J. (2004). Enhanced toxicity and cellular binding of a modified amyloid beta peptide with a methionine to valine substitution. J Biol Chem, 279, 42528-42534.
40. Barnham, K.J., Haeffner, F., Ciccotosto, G.D., Curtain, C.C., Tew, D., Mavros, C., Beyreuther, K., Carrington, D., Masters, C.L., Cherny, R.A., et al. (2004). Tyrosine gated electron transfer is key to the toxic mechanism of Alzheimer's disease betaamyloid. FASEB J, 18, 1427-1429.
41. Haeffner, F., Smith, D.G., Barnham, K.J., Bush, A.I. (2005). Model studies of cholesterol, and ascorbate oxidation by copper complexes: relevance to Alzheimer's disease beta-amyloid metallochemistry. J Inorg Biochem, 99, 2403-2422.
42. Murray, I.V., Sindoni, M.E., Axelsen, P.H. (2005). Promotion of oxidative lipid membrane damage by amyloid beta proteins. Biochemistry, 44, 12606-12613.
43. Puglielli, L., Friedlich, A.L., Setchell, K.D.R., Nagano, S., Opazo, C., Cherny, R.A., Barnham, K.J., Wade, J.D., Melov, S., Kovacs, D.M., Bush, A.I. (2005). Cholesterol oxidase mimetic activity of Alzheimer's disease b-amyloid. J Clin Invest, 115, 2556-2563.
44. Smith, D.P., Smith, D.G., Curtain, C.C., Boas, J.F., Pilbrow, J.R., Ciccotosto, G.D., Lau, T.L., Tew, D.J., Perez, K., Wade, J.D., et al. (2006). Copper-mediated amyloidbeta toxicity is associated with an intermolecular histidine bridge. J Biol Chem, 281, 15145-15154.
45. Markesbery, W.R., Lovell, M.A. (2007). Damage to lipids, proteins, DNA, and RNA in mild cognitive impairment. Arch Neurol, 64, 954-956.
46. Smith, M.A., Perry, G., Richey, P.L., Sayre, L.M., Anderson, V.E., Beal, M.F., Kowall, N. (1996). Oxidative damage in Alzheimer's. Nature, 382, 120-121.
47. Smith, M.A., Richey Harris, P.L., Sayre, L.M., Beckman, J.S., Perry, G. (1997). Widespread peroxynitrite-mediated damage in Alzheimer's disease. J.Neurosci, 17, 2653-2657.
48. Kang, J., Lemaire, H.G., Unterbeck, A., Salbaum, J.M., Masters, C.L., Grzeschik, K.H., Multhaup, G., Beyreuther, K., Muller-Hill, B. (1987). The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature, 325, 733-736.
49. Masters, C.L., Simms, G., Weinman, N.A., Multhaup, G., McDonald, B.L., Beyreuther, K. (1985). Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A, 82, 4245-4249.
50. Huang, X., Cuajungco, M.P., Atwood, C.S., Hartshorn, M.A., Tyndall, J.D., Hanson, G.R., Stokes, K.C., Leopold, M., Multhaup, G., Goldstein, L.E., et al. (1999). Cu(II) potentiation of Alzheimer Abeta neurotoxicity: correlation with cellfree hydrogen peroxide production and metal reduction, J Biol Chem, 274, 37111-37116.
51. Abramov, A.Y., Canevari, L., Duchen, M.R. (2003). Changes in intracellular calcium and glutathione in astrocytes as the primary mechanism of amyloid neurotoxicity. J Neurosci, 23, 5088-5095.
52. Chen, K., Kazachkov, M., Yu, P.H. (2007). Effect of aldehydes derived from oxidative deamination and oxidative stress on beta-amyloid aggregation; pathological implications to Alzheimer's disease. J Neural Transm, 114, 835-839.
53. Hensley, K., Maidt, M.L., Yu, Z., Sang, H., Markesbery, W.R., Floyd, R.A. (1998). Electrochemical analysis of protein nitrotyrosine and dityrosine in the Alzheimer brain indicates region-specific accumulation. J Neurosci, 18, 8126-8132.
54. Reynolds, M.R., Berry, R.W., Binder, L.I. (2005). Site-specific nitration differentially influences tau assembly in vitro. Biochemistry, 44, 13997-14009.
55. Maeda, J., Ji, B., Irie, T., Tomiyama, T., Maruyama, M., Okauchi, T., Staufenbiel, M., Iwata, N., Ono, M., Saido, T.C., et al. (2007). Longitudinal, quantitative assessment of amyloid, neuroinflammation, and anti-amyloid treatment in a living mouse model of Alzheimer's disease enabled by positron emission tomography. J Neurosci, 27, 10957-10968.
56. Shankar, G.M., Li, S., Mehta, T.H., Garcia-Munoz, A., Shepardson, N.E., Smith, I., Brett, F.M., Farrell, M.A., Rowan, M.J., Lemere, C.A., et al. (2008). Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat Med, 14, 837-842.
57. Lesne, S., Koh, M.T., Kotilinek, L., Kayed, R., Glabe, C.G., Yang, A., Gallagher, M., Ashe, K.H. (2006). A specific amyloid-beta protein assembly in the brain impairs memory. Nature, 440, 352-357.
58. Friedlich, A.L., Lee, J.Y., van Groen, T., Cherny, R.A., Volitakis, I., Cole, T.B., Palmiter, R.D., Koh, J.Y., Bush, A.I. (2004). Neuronal zinc exchange with the blood vessel wall promotes cerebral amyloid angiopathy in an animal model of Alzheimer's disease. J Neurosci, 24, 3453-3459.
59. Lee, J.Y., Friedman, J.E., Angel, I., Kozak, A., Koh, J.Y. (2004). The lipophilic metal chelator DP-109 reduces amyloid pathology in brains of human beta-amyloid precursor protein transgenic mice. Neurobiol Aging, 25, 1315-1321.
60. Lovell, M.A., Robertson, J.D., Teesdale, W.J., Campbell, J.L., Markesbery, W.R. (1998). Copper, iron and zinc in Alzheimer's disease senile plaques. J Neurol Sci, 158, 47-52.
61. Miller, L.M., Wang, Q., Telivala, T.P., Smith, R.J., Lanzirotti, A., Miklossy, J. (2006). Synchrotron-based infrared and x-ray imaging shows focalized accumulation of Cu and Zn co-localized with beta-amyloid deposits in Alzheimer's disease. J Struct Biol, 155, 30-37.
62. Stoltenberg, M., Bruhn, M., Sondergaard, C., Doering, P., West, M.J., Larsen, A., Troncoso, J.C., Danscher, G. (2005). Immersion autometallographic tracing of zinc ions in Alzheimer beta-amyloid plaques. Histochem Cell Biol, 123, 605-611.
63. Stoltenberg, M., Bush, A.I., Bach, G., Smidt, K., Larsen, A., Rungby, J., Lund, S., Doering, P., Danscher, G. (2007). Amyloid plaques arise from zinc-enriched cortical layers in APP/PS1 transgenic mice and are paradoxically enlarged with dietary zinc deficiency. Neuroscience, 150, 357-369.
64. Suh, S.W., Jensen, K.B., Jensen, M.S., Silva, D.S., Kesslak, P.J., Danscher, G., Frederickson, C.J. (2000). Histochemically-reactive zinc in amyloid plaques, angiopathy, and degenerating neurons of Alzheimer's diseased brains. Brain Res, 852, 274-278.
65. Grundke-Iqbal, I., Fleming, J., Tung, Y.C., Lassmann, H., Iqbal, K., Joshi, J.G. (1990). Ferritin is a component of the neuritic (senile) plaque in Alzheimer dementia. Acta Neuropathol, 81, 105-110.
66. Cole, T.B., Wenzel, H.J., Kafer, K.E., Schwartzkroin, P.A., Palmiter, R.D. (1999). Elimination of zinc from synaptic vesicles in the intact mouse brain by disruption of the ZnT3 gene. Proc Natl Acad Sci U S A, 96, 1716-1721.
67. Lee, J.-Y., Cole, T.B., Palmiter, R.D., Suh, S.W., Koh, J.-Y. (2002). Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice. Proc Natl Acad Sci U S A, 99, 7705-7710.
68. Bush, A.I., Tanzi, R.E. (2002). The galvanization of beta-amyloid in Alzheimer's disease. Proc Natl Acad Sci U S A, 99, 7317-7319.
69. Terry, R.D., Masliah, E., Salmon, D.P., Butters, N., DeTeresa, R., Hill, R., Hansen, L.A., Katzman, R. (1991). Physical basis of cognitive alterations in Alzheimer's disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol, 30, 572-580.
70. Schlief, M.L., Craig, A.M., Gitlin, J.D. (2005). NMDA receptor activation mediates copper homeostasis in hippocampal neurons. J Neurosci, 25, 239-246.
71. Schlief, M.L., West, T., Craig, A.M., Holtzman, D.M., Gitlin, J.D. (2006). Role of the Menkes copper-transporting ATPase in NMDA receptor-mediated neuronal toxicity. Proc Natl Acad Sci U S A, 103, 14919-14924.
72. Religa, D., Strozyk, D., Cherny, R.A., Volitakis, I., Haroutunian, V., Winblad, B., Naslund, J., Bush, A.I. (2006). Elevated cortical zinc in Alzheimer disease. Neurology, 67, 69-75.
73. Bayer, T.A., Schafer, S., Simons, A., Kemmling, A., Kamer, T., Tepests, R., Eckert, A., Schussel, K., Eikenberg, O., Sturchler-Pierrat, C., et al. (2003). Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid A{beta} production in APP23 transgenic mice, Proc Natl Acad Sci U S A, 100, 14187-14192.
74. Phinney, A.L., Drisaldi, B., Schmidt, S.D., Lugowski, S., Coronado, V., Liang, Y., Horne, P., Yang, J., Sekoulidis, J., Coomaraswamy, J., et al. (2003). In vivo reduction of amyloid-{beta} by a mutant copper transporter. Proc Natl Acad Sci U S A, 100, 14193-14198.
75. Morris, M.C., Evans, D.A., Tangney, C.C., Bienias, J.L., Schneider, J.A., Wilson, R.S., Scherr, P.A. (2006). Dietary copper and high saturated and trans fat intakes associated with cognitive decline. Arch Neurol, 63, 1085-1088.
76. Zhang, J., Liu, Q., Chen, Q., Liu, N.Q., Li, F.L., Lu, Z.B., Qin, C., Zhu, H., Huang, Y.Y., He, W., Zhao, B.L. (2006). Nicotine attenuates beta-amyloid-induced neurotoxicity by regulating metal homeostasis. FASEB J, 20, 1212-1214.
77. Crapper McLachlan, D.R., Dalton, A.J., Kruck, T.P.A., Bell, M.Y., Smith, W.L., Kalow, W., Andrews, D.F. (1991). Intramuscular desferrioxamine in patients with Alzheimer's disease. Lancet, 337, 1304-1308.
78. Squitti, R., Rossini, P.M., Cassetta, E., Moffa, F., Pasqualetti, P., Cortesi, M., Colloca, A., Rossi, L., Finazzi-Agro, A. (2002). D-Penicillamine reduces serum oxidative stress in Alzheimer's disease patients. Eur J Clin Invest, 32, 51-59.
79. Cherny, R.A., Atwood, C.S., Xilinas, M.E., Gray, D.N., Jones, W.D., McLean, C.A., Barnham, K.J., Volitakis, I., Fraser, F.W., et al. (2001). Treatment with a copper-zinc chelator markedly and rapidly inhibits b-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron, 30, 665-676.
80. Ritchie, C.W., Bush, A.I., Mackinnon, A., Macfarlane, S., Mastwyk, M., MacGregor, L., Kiers, L., Cherny, R., Li, Q.X., Tammer, A., et al. (2003). Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Arch Neurol, 60, 1685-1691.
81. Lannfelt, L., Blennow, K., Zetterberg, H., Batsman, S., Ames, D., Harrison, J., Masters, C.L., Targum, S., Bush, A.I., Murdoch, R., et al. (2008). Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial. Lancet Neurol, 7, 779-786.
82. Adlard, P.A., Cherny, R.A., Finkelstein, D.I., Gautier, E., Robb, E., Cortes, M., Volitakis, I., Liu, X., Smith, J.P., Perez, K., et al. (2008). Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta. Neuron, 59, 43-55.
83. White, A.R., Du, T., Laughton, K.M., Volitakis, I., Sharples, R.A., Xilinas, M.E., Hoke, D.E., Holsinger, R.M., Evin, G., Cherny, R.A., et al. (2006). Degradation of the Alzheimer disease amyloid beta-peptide by metal-dependent up-regulation of metalloprotease activity. J Biol Chem, 281, 17670-17680.
84. Kaur, D., Yantiri, F., Kumar, J., Mo, J.O., Rajagopalan, S., Viswanath, V., Boonplueang, R., Jacobs, R., Yang, L., Beal, M.F., et al. (2003). Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease. Neuron, 37, 923-933.
85. Nguyen, T., Hamby, A., Massa, S.M. (2005). Clioquinol down-regulates mutant huntingtin expression in vitro and mitigates pathology in a Huntington's disease mouse model. Proc Natl Acad Sci U S A, 102, 11840-11845.
86. Fox, J.H., Kama, J.A., Lieberman, G., Chopra, R., Dorsey, K., Chopra, V., Volitakis, I., Cherny, R.A., Bush, A.I., Hersch, S. (2007). Mechanisms of copper ion mediated Huntington's disease progression. PLoS ONE, 2, e334.