New therapeutic targets in Alzheimer's disease: Brain deregulation of calcium and zinc

Cell Death and Disease

Volumn 2, Issue 6, 2011, Pages

  Corona, C ^a,b   Pensalfini, A ^c   Frazzini, V ^a   Sensi, S L ^a,d  

^a UNIVERSITY OF CHIETI   (Italy)

^b NewYork Presbyterian Hospital   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Alzheimer's disease; Calcium; Glutamate; Oxidative stress; Zinc

Indexed keywords

AMYLOID BETA PROTEIN; CALCIUM; CATION; DP 109; EVT 101; FREE RADICAL; GLUTAMIC ACID; IFENPRODIL; MEMANTINE; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2A; RO 256981; TACROLIMUS; TAU PROTEIN; UNCLASSIFIED DRUG; ZINC;

ALZHEIMER DISEASE; CALCIUM HOMEOSTASIS; CENTRAL NERVOUS SYSTEM; DRUG TARGETING; HUMAN; NERVE CELL PLASTICITY; NEUROTRANSMISSION; NONHUMAN; PRIORITY JOURNAL; PROTEIN METABOLISM; PROTEIN PHOSPHORYLATION; REVIEW; SYNAPTIC TRANSMISSION; UNSPECIFIED SIDE EFFECT; ANIMAL; BRAIN; DRUG EFFECT; METABOLISM; METHODOLOGY; MOLECULARLY TARGETED THERAPY;

ALZHEIMER DISEASE; ANIMALS; BRAIN; CALCIUM; HUMANS; MOLECULAR TARGETED THERAPY; ZINC;

EID: 79960017316     PISSN: None     EISSN: 20414889     Source Type: Journal    
DOI: 10.1038/cddis.2011.57     Document Type: Review

References (118)

1. Sensi SL, Paoletti P, Bush AI, Sekler I. Zinc in the physiology and pathology of the CNS. Nat Rev Neurosci 2009; 10: 780-791.
2. Green KN, LaFerla FM. Linking calcium to Abeta and Alzheimer's disease. Neuron 2008; 59: 190-194. (Pubitemid 352033693)
3. Mattson MP. ER calcium and Alzheimer's disease: in a state of flux. Sci Signal 2010; 3: pe10.
4. Qian J, Noebels JL. Visualization of transmitter release with zinc fluorescence detection at the mouse hippocampal mossy fibre synapse. J Physiol 2005; 566 (Pt 3): 747-758. (Pubitemid 41122658)
5. Lannfelt L, Blennow K, Zetterberg H, Batsman S, Ames D, Harrison J et al. 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 2008; 7: 779-786.
6. Faux NG, Ritchie CW, Gunn A, Rembach A, Tsatsanis A, Bedo J et al. PBT2 rapidly improves cognition in Alzheimer's Disease: additional phase II analyses. J Alzheimers Dis 2010; 20: 509-516.
7. Khachaturian ZS. Calcium, membranes, aging, and Alzheimer's disease. Introduction and overview. Ann NY Acad Sci 1989; 568: 1-4. (Pubitemid 20166513)
8. Kuchibhotla KV, Goldman ST, Lattarulo CR, Wu HY, Hyman BT, Bacskai BJ. Abeta plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks. Neuron 2008; 59: 214-225. (Pubitemid 352033686)
9. Tu H, Nelson O, Bezprozvanny A, Wang Z, Lee SF, Hao YH et al. Presenilins form ER Ca2+ leak channels, a function disrupted by familial Alzheimer's disease-linked mutations. Cell 2006; 126: 981-993. (Pubitemid 44310781)
10. Green KN, Demuro A, Akbari Y, Hitt BD, Smith IF, Parker I et al. SERCA pump activity is physiologically regulated by presenilin and regulates amyloid beta production. J Gen Physiol 2008; 132: i1.
11. Cheung KH, Shineman D, Muller M, Cardenas C, Mei L, Yang J et al. Mechanism of Ca2+ disruption in Alzheimer's disease by presenilin regulation of InsP3 receptor channel gating. Neuron 2008; 58: 871-883. (Pubitemid 351842747)
12. Rybalchenko V, Hwang SY, Rybalchenko N, Koulen P. The cytosolic N-terminus of presenilin-1 potentiates mouse ryanodine receptor single channel activity. Int J Biochem Cell Biol 2008; 40: 84-97. (Pubitemid 350052661)
13. Stutzmann GE, Caccamo A, LaFerla FM, Parker I. Dysregulated IP3 signaling in cortical neurons of knock-in mice expressing an Alzheimer's-linked mutation in presenilin1 results in exaggerated Ca2+ signals and altered membrane excitability. J Neurosci 2004; 24: 508-513. (Pubitemid 38112383)
14. Stutzmann GE, Smith I, Caccamo A, Oddo S, Parker I, Laferla F. Enhanced ryanodinemediated calcium release in mutant PS1-expressing Alzheimer's mouse models. Ann NY Acad Sci 2007; 1097: 265-277. (Pubitemid 47084900)
15. Zampese E, Fasolato C, Kipanyula MJ, Bortolozzi M, Pozzan T, Pizzo P. Presenilin 2 modulates endoplasmic reticulum (ER)-mitochondria interactions and Ca2+ cross-talk. Proc Natl Acad Sci USA 2011; 108: 2777-2782.
16. Yoo AS, Cheng I, Chung S, Grenfell TZ, Lee H, Pack-Chung E et al. Presenilin-mediated modulation of capacitative calcium entry. Neuron 2000; 27: 561-572.
17. Leissring MA, Akbari Y, Fanger CM, Cahalan MD, Mattson MP, LaFerla FM. Capacitative calcium entry deficits and elevated luminal calcium content in mutant presenilin-1 knockin mice. J Cell Biol 2000; 149: 793-798.
18. Scheuner D, Eckman C, Jensen M, Song X, Citron M, Suzuki N et al. Secreted amyloid beta-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease. Nat Med 1996; 2: 864-870. (Pubitemid 26296755)
19. Rojas G, Cardenas AM, Fernandez-Olivares P, Shimahara T, Segura-Aguilar J, Caviedes R et al. Effect of the knockdown of amyloid precursor protein on intracellular calcium increases in a neuronal cell line derived from the cerebral cortex of a trisomy 16 mouse. Exp Neurol 2008; 209: 234-242.
20. Lopez JR, Lyckman A, Oddo S, Laferla FM, Querfurth HW, Shtifman A. Increased intraneuronal resting [Ca2+] in adult Alzheimer's disease mice. J Neurochem 2008; 105: 262-271. (Pubitemid 351441642)
21. Herms J, Schneider I, Dewachter I, Caluwaerts N, Kretzschmar H, Van Leuven F. Capacitive calcium entry is directly attenuated by mutant presenilin-1, independent of the expression of the amyloid precursor protein. J Biol Chem 2003; 278: 2484-2489. (Pubitemid 36801325)
22. Stieren E, Werchan WP, El Ayadi A, Li F, Boehning D. FAD mutations in amyloid precursor protein do not directly perturb intracellular calcium homeostasis. PLoS One 2010; 5: e11992.
23. Veinbergs I, Everson A, Sagara Y, Masliah E. Neurotoxic effects of apolipoprotein E4 are mediated via dysregulation of calcium homeostasis. J Neurosci Res 2002; 67: 379-387. (Pubitemid 34137145)
24. Dreses-Werringloer U, Lambert JC, Vingtdeux V, Zhao H, Vais H, Siebert A et al. A polymorphism in CALHM1 influences Ca2+ homeostasis, Abeta levels, and Alzheimer's disease risk. Cell 2008; 133: 1149-1161. (Pubitemid 351863682)
25. Buxbaum JD, Ruefli AA, Parker CA, Cypess AM, Greengard P. Calcium regulates processing of the Alzheimer amyloid protein precursor in a protein kinase C-independent manner. Proc Natl Acad Sci USA 1994; 91: 4489-4493. (Pubitemid 24143459)
26. Hoey SE, Williams RJ, Perkinton MS. Synaptic NMDA receptor activation stimulates alpha-secretase amyloid precursor protein processing and inhibits amyloid-beta production. J Neurosci 2009; 29: 4442-4460.
27. Petryniak MA, Wurtman RJ, Slack BE. Elevated intracellular calcium concentration increases secretory processing of the amyloid precursor protein by a tyrosine phosphorylation-dependent mechanism. Biochem J 1996; 320 (Pt 3): 957-963. (Pubitemid 27013815)
28. Querfurth HW, Selkoe DJ. Calcium ionophore increases amyloid beta peptide production by cultured cells. Biochemistry 1994; 33: 4550-4561. (Pubitemid 24145103)
29. Chakroborty S, Goussakov I, Miller MB, Stutzmann GE. Deviant ryanodine receptormediated calcium release resets synaptic homeostasis in presymptomatic 3×Tg-AD mice. J Neurosci 2009; 29: 9458-9470.
30. Nimmrich V, Grimm C, Draguhn A, Barghorn S, Lehmann A, Schoemaker H et al. Amyloid beta oligomers (A beta(1-42) globulomer) suppress spontaneous synaptic activity by inhibition of P/Q-type calcium currents. J Neurosci 2008; 28: 788-797. (Pubitemid 351159014)
31. Ueda K, Shinohara S, Yagami T, Asakura K, Kawasaki K. Amyloid beta protein potentiates Ca2+ influx through L-type voltage-sensitive Ca2+ channels: a possible involvement of free radicals. J Neurochem 1997; 68: 265-271. (Pubitemid 26427316)
32. Supnet C, Grant J, Kong H, Westaway D, Mayne M. Amyloid-beta-(1-42) increases ryanodine receptor-3 expression and function in neurons of TgCRND8 mice. J Biol Chem 2006; 281: 38440-38447. (Pubitemid 46041967)
33. Niu Y, Su Z, Zhao C, Song B, Zhang X, Zhao N et al. Effect of amyloid beta on capacitive calcium entry in neural 2a cells. Brain Res Bull 2009; 78: 152-157.
34. Wu HY, Hudry E, Hashimoto T, Kuchibhotla K, Rozkalne A, Fan Z et al. Amyloid beta induces the morphological neurodegenerative triad of spine loss, dendritic simplification, and neuritic dystrophies through calcineurin activation. J Neurosci 2010; 30: 2636-2649.
35. Rozkalne A, Hyman BT, Spires-Jones TL. Calcineurin inhibition with FK506 ameliorates dendritic spine density deficits in plaque-bearing Alzheimer model mice. Neurobiol Dis 2011; 41: 650-654.
36. Arispe N, Rojas E, Pollard HB. Alzheimer disease amyloid beta protein forms calcium channels in bilayer membranes: blockade by tromethamine and aluminum. Proc Natl Acad Sci USA 1993; 90: 567-571. (Pubitemid 23028904)
37. Diaz JC, Simakova O, Jacobson KA, Arispe N, Pollard HB. Small molecule blockers of the Alzheimer Abeta calcium channel potently protect neurons from Abeta cytotoxicity. Proc Natl Acad Sci USA 2009; 106: 3348-3353.
38. DeKosky ST, Scheff SW. Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity. Ann Neurol 1990; 27: 457-464. (Pubitemid 20149963)
39. Hsia AY, Masliah E, McConlogue L, Yu GQ, Tatsuno G, Hu K et al. Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc Natl Acad Sci USA 1999; 96: 3228-3233. (Pubitemid 29148873)
40. Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D, Iwatsubo T et al. APP processing and synaptic function. Neuron 2003; 37: 925-937. (Pubitemid 36398299)
41. Mucke L, Masliah E, Yu GQ, Mallory M, Rockenstein EM, Tatsuno G et al. High-level neuronal expression of abeta 1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation. J Neurosci 2000; 20: 4050-4058. (Pubitemid 30365675)
42. Cirrito JR, May PC, O'Dell MA, Taylor JW, Parsadanian M, Cramer JW et al. In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-beta metabolism and half-life. J Neurosci 2003; 23: 8844-8853. (Pubitemid 37210896)
43. Abramov E, Dolev I, Fogel H, Ciccotosto GD, Ruff E, Slutsky I. Amyloid-beta as a positive endogenous regulator of release probability at hippocampal synapses. Nat Neurosci 2009; 12: 1567-1576.
44. Hsieh H, Boehm J, Sato C, Iwatsubo T, Tomita T, Sisodia S et al. AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron 2006; 52: 831-843. (Pubitemid 44828454)
45. Shankar GM, Bloodgood BL, Townsend M, Walsh DM, Selkoe DJ, Sabatini BL. Natural oligomers of the Alzheimer amyloid-beta protein induce reversible synapse loss by modulating an NMDA-type glutamate receptor-dependent signaling pathway. J Neurosci 2007; 27: 2866-2875. (Pubitemid 46438992)
46. Snyder EM, Nong Y, Almeida CG, Paul S, Moran T, Choi EY et al. Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci 2005; 8: 1051-1058. (Pubitemid 41061516)
47. Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS et al. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 2002; 416: 535-539. (Pubitemid 34288854)
48. Wei W, Nguyen LN, Kessels HW, Hagiwara H, Sisodia S, Malinow R. Amyloid beta from axons and dendrites reduces local spine number and plasticity. Nat Neurosci 2010; 13: 190-196.
49. Collingridge GL, Peineau S, Howland JG, Wang YT. Long-term depression in the CNS. Nat Rev Neurosci 2010; 11: 459-473.
50. Nagerl UV, Eberhorn N, Cambridge SB, Bonhoeffer T. Bidirectional activity-dependent morphological plasticity in hippocampal neurons. Neuron 2004; 44: 759-767. (Pubitemid 39575630)
51. De Felice FG, Velasco PT, Lambert MP, Viola K, Fernandez SJ, Ferreira ST et al. Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptordependent mechanism that is blocked by the Alzheimer drug memantine. J Biol Chem 2007; 282: 11590-11601. (Pubitemid 47100810)
52. Molnar Z, Soos K, Lengyel I, Penke B, Szegedi V, Budai D. Enhancement of NMDA responses by beta-amyloid peptides in the hippocampus in vivo. Neuroreport 2004; 15: 1649-1652. (Pubitemid 38971187)
53. Zhao WQ, Santini F, Breese R, Ross D, Zhang XD, Stone DJ et al. Inhibition of calcineurin-mediated endocytosis and alpha-amino-3-hydroxy-5- methyl-4- isoxazolepropionic acid (AMPA) receptors prevents amyloid beta oligomer-induced synaptic disruption. J Biol Chem 2010; 285: 7619-7632.
54. Billings LM, Oddo S, Green KN, McGaugh JL, LaFerla FM. Intraneuronal Abeta causes the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice. Neuron 2005; 45: 675-688. (Pubitemid 40320703)
55. Pierrot N, Santos SF, Feyt C, Morel M, Brion JP, Octave JN. Calcium-mediated transient phosphorylation of tau and amyloid precursor protein followed by intraneuronal amyloidbeta accumulation. J Biol Chem 2006; 281: 39907-39914. (Pubitemid 46041794)
56. Tampellini D, Capetillo-Zarate E, Dumont M, Huang Z, Yu F, Lin MT et al. Effects of synaptic modulation on beta-amyloid, synaptophysin, and memory performance in Alzheimer's disease transgenic mice. J Neurosci 2010; 30: 14299-14304.
57. Tampellini D, Rahman N, Gallo EF, Huang Z, Dumont M, Capetillo-Zarate E et al. Synaptic activity reduces intraneuronal Abeta, promotes APP transport to synapses, and protects against Abeta-related synaptic alterations. J Neurosci 2009; 29: 9704-9713.
58. Pimplikar SW, Nixon RA, Robakis NK, Shen J, Tsai LH. Amyloid-independent mechanisms in Alzheimer's disease pathogenesis. J Neurosci 2010; 30: 14946-14954.
59. Gotz J, Nitsch RM. Compartmentalized tau hyperphosphorylation and increased levels of kinases in transgenic mice. Neuroreport 2001; 12: 2007-2016. (Pubitemid 32553723)
60. Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J et al. Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell 2010; 142: 387-397.
61. Zempel H, Thies E, Mandelkow E, Mandelkow EM. Abeta oligomers cause localized Ca(2+) elevation, missorting of endogenous Tau into dendrites, Tau phosphorylation, and destruction of microtubules and spines. J Neurosci 2010; 30: 11938-11950.
62. Gotz J, Chen F, van Dorpe J, Nitsch RM. Formation of neurofibrillary tangles in P301 l tau transgenic mice induced by Abeta 42 fibrils. Science 2001; 293: 1491-1495. (Pubitemid 32807681)
63. Sydow A, Van der Jeugd A, Zheng F, Ahmed T, Balschun D, Petrova O et al. Tau-induced defects in synaptic plasticity, learning, and memory are reversible in transgenic mice after switching off the toxic Tau mutant. J Neurosci 2011; 31: 2511-2525.
64. Shipton OA, Leitz JR, Dworzak J, Acton CE, Tunbridge EM, Denk F et al. Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation. J Neurosci 2011; 31: 1688-1692.
65. Park SY, Ferreira A. The generation of a 17 kDa neurotoxic fragment: an alternative mechanism by which tau mediates beta-amyloid-induced neurodegeneration. J Neurosci 2005; 25: 5365-5375. (Pubitemid 40770916)
66. Garg S, Timm T, Mandelkow EM, Mandelkow E, Wang Y. Cleavage of Tau by calpain in Alzheimer's disease: the quest for the toxic 17 kD fragment. Neurobiol Aging 2011; 32: 1-14.
67. Harris ME, Wang Y, Pedigo Jr NW, Hensley K, Butterfield DA, Carney JM. Amyloid beta peptide (25-35) inhibits Na+-dependent glutamate uptake in rat hippocampal astrocyte cultures. J Neurochem 1996; 67: 277-286. (Pubitemid 26185607)
68. Melov S, Adlard PA, Morten K, Johnson F, Golden TR, Hinerfeld D et al. Mitochondrial oxidative stress causes hyperphosphorylation of tau. PLoS One 2007; 2: e536.
69. Jin M, Shepardson N, Yang T, Chen G, Walsh D, Selkoe DJ. Soluble amyloid {beta}- protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration. Proc Natl Acad Sci USA 2011; 108: 5819-5824.
70. Sensi SL, Ton-That D, Sullivan PG, Jonas EA, Gee KR, Kaczmarek LK et al. Modulation of mitochondrial function by endogenous Zn2+ pools. Proc Natl Acad Sci USA 2003; 100: 6157-6162. (Pubitemid 36576947)
71. Velazquez RA, Cai Y, Shi Q, Larson AA. The distribution of zinc selenite and expression of metallothionein-III mRNA in the spinal cord and dorsal root ganglia of the rat suggest a role for zinc in sensory transmission. J Neurosci 1999; 19: 2288-2300. (Pubitemid 29133404)
72. Wang Z, Li JY, Dahlstrom A, Danscher G. Zinc-enriched GABAergic terminals in mouse spinal cord. Brain Res 2001; 921: 165-172. (Pubitemid 33096295)
73. Hirzel K, Muller U, Latal AT, Hulsmann S, Grudzinska J, Seeliger MW et al. Hyperekplexia phenotype of glycine receptor alpha1 subunit mutant mice identifies Zn(2+) as an essential endogenous modulator of glycinergic neurotransmission. Neuron 2006; 52: 679-690.
74. Mayer ML, Vyklicky Jr L. The action of zinc on synaptic transmission and neuronal excitability in cultures of mouse hippocampus. J Physiol 1989; 415: 351-365. (Pubitemid 19205516)
75. Christine CW, Choi DW. Effect of zinc on NMDA receptor-mediated channel currents in cortical neurons. J Neurosci 1990; 10: 108-116. (Pubitemid 20059246)
76. Legendre P, Westbrook GL. The inhibition of single N-methyl-D-aspartate- activated channels by zinc ions on cultured rat neurones. J Physiol 1990; 429: 429-449. (Pubitemid 20327560)
77. Zheng F, Gingrich MB, Traynelis SF, Conn PJ. Tyrosine kinase potentiates NMDA receptor currents by reducing tonic zinc inhibition. Nat Neurosci 1998; 1: 185-191.
78. Rassendren FA, Lory P, Pin JP, Nargeot J. Zinc has opposite effects on NMDA and non-NMDA receptors expressed in Xenopus oocytes. Neuron 1990; 4: 733-740. (Pubitemid 20185088)
79. Corona C, Masciopinto F, Silvestri E, Viscovo AD, Lattanzio R, Sorda RL et al. Dietary zinc supplementation of 3×Tg-AD mice increases BDNF levels and prevents cognitive deficits as well as mitochondrial dysfunction. Cell Death Dis 2010; 1: e91.
80. Besser L, Chorin E, Sekler I, Silverman WF, Atkin S, Russell JT et al. Synaptically released zinc triggers metabotropic signaling via a zinc-sensing receptor in the hippocampus. J Neurosci 2009; 29: 2890-2901.
81. Huang YZ, Pan E, Xiong ZQ, McNamara JO. Zinc-mediated transactivation of TrkB potentiates the hippocampal mossy fiber-CA3 pyramid synapse. Neuron 2008; 57: 546-558. (Pubitemid 351273988)
82. Hwang JJ, Park MH, Choi SY, Koh JY. Activation of the Trk signaling pathway by extracellular zinc. Role of metalloproteinases. J Biol Chem 2005; 280: 11995-12001.
83. Lichtenthaler SF. Alpha-secretase in Alzheimer's disease: molecular identity, regulation and therapeutic potential. J Neurochem 2011; 116: 10-21.
84. Hershfinkel M, Kandler K, Knoch ME, Dagan-Rabin M, Aras MA, Abramovitch-Dahan C et al. Intracellular zinc inhibits KCC2 transporter activity. Nat Neurosci 2009; 12: 725-727.
85. Adlard PA, Parncutt JM, Finkelstein DI, Bush AI. Cognitive loss in zinc transporter-3 knock-out mice: a phenocopy for the synaptic and memory deficits of Alzheimer's disease? J Neurosci 2010; 30: 1631-1636.
86. Sindreu C, Palmiter RD, Storm DR. Zinc transporter ZnT-3 regulates presynaptic Erk1/2 signaling and hippocampus-dependent memory. Proc Natl Acad Sci USA 2011; 108: 3366-3370.
87. Deshpande A, Kawai H, Metherate R, Glabe CG, Busciglio J. A role for synaptic zinc in activity-dependent Abeta oligomer formation and accumulation at excitatory synapses. J Neurosci 2009; 29: 4004-4015.
88. Smith JL, Xiong S, Markesbery WR, Lovell MA. Altered expression of zinc transporters-4 and -6 in mild cognitive impairment, early and late Alzheimer's disease brain. Neuroscience 2006; 140: 879-888.
89. Lyubartseva G, Smith JL, Markesbery WR, Lovell MA. Alterations of zinc transporter proteins ZnT-1, ZnT-4 and ZnT-6 in preclinical Alzheimer's disease brain. Brain Pathol 2010; 20: 343-350.
90. Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, Markesbery WR. Copper, iron and zinc in Alzheimer's disease senile plaques. J Neurol Sci 1998; 158: 47-52. (Pubitemid 28277534)
91. Lee JY, Cole TB, Palmiter RD, Suh SW, Koh JY. Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice. Proc Natl Acad Sci USA 2002; 99: 7705-7710. (Pubitemid 34568755)
92. Bush AI, Pettingell WH, Multhaup G, d Paradis M, Vonsattel JP, Gusella JF et al. Rapid induction of Alzheimer A beta amyloid formation by zinc. Science 1994; 265: 1464-1467. (Pubitemid 24306803)
93. Huang X, Atwood CS, Moir RD, Hartshorn MA, Tanzi RE, Bush AI. Trace metal contamination initiates the apparent auto-aggregation, amyloidosis, and oligomerization of Alzheimer's Abeta peptides. J Biol Inorg Chem 2004; 9: 954-960. (Pubitemid 40109902)
94. Cherny RA, Legg JT, McLean CA, Fairlie DP, Huang X, Atwood CS et al. Aqueous dissolution of Alzheimer's disease Abeta amyloid deposits by biometal depletion. J Biol Chem 1999; 274: 23223-23228.
95. Bush AI, Pettingell Jr WH, Paradis MD, Tanzi RE. Modulation of A beta adhesiveness and secretase site cleavage by zinc. J Biol Chem 1994; 269: 12152-12158.
96. LaFerla FM, Green KN, Oddo S. Intracellular amyloid-beta in Alzheimer's disease. Nat Rev Neurosci 2007; 8: 499-509.
97. Sensi SL, Rapposelli IG, Frazzini V, Mascetra N. Altered oxidant-mediated intraneuronal zinc mobilization in a triple transgenic mouse model of Alzheimer's disease. Exp Gerontol 2008; 43: 488-492.
98. Miller Y, Ma B, Tsai CJ, Nussinov R. Hollow core of Alzheimer's Abeta42 amyloid observed by cryoEM is relevant at physiological pH. Proc Natl Acad Sci USA 2010; 107: 14128-14133.
99. Dong J, Canfield JM, Mehta AK, Shokes JE, Tian B, Childers WS et al. Engineering metal ion coordination to regulate amyloid fibril assembly and toxicity. Proc Natl Acad Sci USA 2007; 104: 13313-13318. (Pubitemid 47293942)
100. Miller Y, Ma B, Nussinov R. Zinc ions promote Alzheimer Abeta aggregation via population shift of polymorphic states. Proc Natl Acad Sci USA 2010; 107: 9490-9495.
101. Sandberg A, Luheshi LM, Sollvander S, Pereira de Barros T, Macao B, Knowles TP et al. Stabilization of neurotoxic Alzheimer amyloid-beta oligomers by protein engineering. Proc Natl Acad Sci USA 2010; 107: 15595-15600.
102. Garai K, Sahoo B, Kaushalya SK, Desai R, Maiti S. Zinc lowers amyloid-beta toxicity by selectively precipitating aggregation intermediates. Biochemistry 2007; 46: 10655-10663. (Pubitemid 47417258)
103. Lovell MA, Xie C, Markesbery WR. Protection against amyloid beta peptide toxicity by zinc. Brain Res 1999; 823: 88-95. (Pubitemid 29225497)
104. Bishop GM, Robinson SR. The amyloid paradox: amyloid-beta-metal complexes can be neurotoxic and neuroprotective. Brain Pathol 2004; 14: 448-452. (Pubitemid 39524973)
105. Cuajungco MP, Faget KY. Zinc takes the center stage: its paradoxical role in Alzheimer's disease. Brain Res Brain Res Rev 2003; 41: 44-56. (Pubitemid 36044593)
106. Mo ZY, Zhu YZ, Zhu HL, Fan JB, Chen J, Liang Y. Low micromolar zinc accelerates the fibrillization of human tau via bridging of Cys-291 and Cys-322. J Biol Chem 2009; 284: 34648-34657.
107. Suh SW, Jensen KB, Jensen MS, Silva DS, Kesslak PJ, Danscher G et al. Histochemically-reactive zinc in amyloid plaques, angiopathy, and degenerating neurons of Alzheimer's diseased brains. Brain Res 2000; 852: 274-278. (Pubitemid 30035163)
108. Boom A, Authelet M, Dedecker R, Frederick C, Van Heurck R, Daubie V et al. Bimodal modulation of tau protein phosphorylation and conformation by extracellular Zn2+ in human-tau transfected cells. Biochim Biophys Acta 2009; 1793: 1058-1067.
109. Sensi SL, Yin HZ, Carriedo SG, Rao SS, Weiss JH. Preferential Zn2+ influx through Ca2+-permeable AMPA/kainate channels triggers prolonged mitochondrial superoxide production. Proc Natl Acad Sci USA 1999; 96: 2414-2419. (Pubitemid 29117929)
110. Lovell MA, Xiong S, Xie C, Davies P, Markesbery WR. Induction of hyperphosphorylated tau in primary rat cortical neuron cultures mediated by oxidative stress and glycogen synthase kinase-3. J Alzheimers Dis 2004; 6: 659-671; discussion 673-681. (Pubitemid 40164172)
111. Ho M, Hoke DE, Chua YJ, Li QX, Culvenor JG, Masters C et al. Effect of metal chelators on gamma-secretase indicates that calcium and magnesium ions facilitate cleavage of alzheimer amyloid precursor substrate. Int J Alzheimers Dis 2010; 2011: 950932.
112. Song MS, Rauw G, Baker GB, Kar S. Memantine protects rat cortical cultured neurons against beta-amyloid-induced toxicity by attenuating tau phosphorylation. Eur J Neurosci 2008; 28: 1989-2002.
113. Martinez-Coria H, Green KN, Billings LM, Kitazawa M, Albrecht M, Rammes G et al. Memantine improves cognition and reduces Alzheimer's-like neuropathology in transgenic mice. Am J Pathol 2010; 176: 870-880.
114. Bakchine S, Loft H. Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study. J Alzheimers Dis 2008; 13: 97-107. (Pubitemid 351365621)
115. Hu NW, Klyubin I, Anwyl R, Rowan MJ. GluN2B subunit-containing NMDA receptor antagonists prevent Abeta-mediated synaptic plasticity disruption in vivo. Proc Natl Acad Sci USA 2009; 106: 20504-20509.
116. Adlard PA, Bica L, White AR, Nurjono M, Filiz G, Crouch PJ et al. Metal ionophore treatment restores dendritic spine density and synaptic protein levels in a mouse model of Alzheimer's disease. PLoS One 2011; 6: e17669.
117. Adlard PA, Cherny RA, Finkelstein DI, Gautier E, Robb E, Cortes M et al. Rapid restoration of cognition in Alzheimer's transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta. Neuron 2008; 59: 43-55. (Pubitemid 351905863)
118. Lee JY, Friedman JE, Angel I, Kozak A, Koh JY. The lipophilic metal chelator DP-109 reduces amyloid pathology in brains of human beta-amyloid precursor protein transgenic mice. Neurobiol Aging 2004; 25: 1315-1321. (Pubitemid 39299169)