416
Views
55
CrossRef citations to date
0
Altmetric
Original

Role of zinc in ALS

&
Pages 131-143 | Received 15 Feb 2006, Accepted 30 Jan 2007, Published online: 10 Jul 2009

References

  • Ferrante R. J., Browne S. E., Shinobu L. A., Bowling A. C., Baik M. J., MacGarvey U., et al. Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis. J Neurochem 1997; 69: 2064–74
  • Liu R., Althaus J. S., Ellerbock B. R., Becker D. A., Gurney M. E. Enhanced oxygen radical production in a transgenic mouse model of familial amyotrophic lateral sclerosis. Ann Neurol 1998; 44: 763–70
  • Pedersen W. A., Fu W., Keller J. N., Markesbery W. R., Appel S., Smith R. G., et al. Protein modification by the lipid peroxidation product 4‐hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients. Ann Neurol 1998; 44: 819–24
  • Shibata N. Transgenic mouse model for familial amyotrophic lateral sclerosis with superoxide dismutase‐1 mutation. Neuropathol 2001; 21: 82–92
  • Chung Y. H., Joo K. M., Lee Y. J., Kim M. J., Cha C. I. Immunohistochemical study on the aggregation of ubiquitin in the central nervous system of transgenic mice expressing a human Cu/Zn SOD mutation. Neurol Res 2003; 25: 395–400
  • Almer G., Vukosavic S., Romero N., Przedborski S. Inducible nitric oxide synthase up‐regulation in a transgenic mouse model of familial amyotrophic lateral sclerosis. J Neurochem 1999; 72: 2415–25
  • Jokic N., Di Scala F., Dupuis L., Rene F., Muller A., De Aguilar J. L., et al. Early activation of antioxidant mechanisms in muscle of mutant Cu/Zn‐superoxide dismutase‐linked amyotrophic lateral sclerosis mice. Ann N.Y. Acad Sci 2003; 1010: 552–8
  • Chen L. ‐C., Smith A. P., Ben Y., Zukic B., Ignacio S., Moore D., et al. Temporal gene expression patterns in G93A/SOD1 mouse. Amyotroph Lateral Scler Other Motor Neuron Disord 2004; 11: 1–8
  • Kiaei M., Kipiani K., Petri S., Choi D. K., Chen J., Calingasan N. Y., et al. Integrative role of cPLA with COX‐2 and the effect of non‐steroidal anti‐inflammatory drugs in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurochem 2005; 93: 403–11
  • Klivenyi P., Kiaei M., Gardian G., Calingasan N. Y., Beal M. F. Additive neuroprotective effects of creatine and cyclooxygenase 2 inhibitors in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurochem 2004; 88: 576–82
  • Shaw P. J., Williams R. Serum and cerebrospinal fluid biochemical markers of ALS. Amyotroph Lateral Scler Other Motor Neuron Disord 2000; 1((Suppl 2))S61–7
  • Sen I., Nalini A., Joshi N. B., Joshi P. G. Cerebrospinal fluid from amyotrophic lateral sclerosis patients preferentially elevates intracellular calcium and toxicity in motor neurons via AMPA/kainate receptor. J Neurol Sci 2005; 235: 45–54
  • Lin C. I., Bristol L. A., Jin L., Dykes‐Hoberg M., Crawford T., Clawson L., et al. Aberrant RNA processing in a neurodegenerative disease: the cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis. Neuron 1988; 20: 589–602
  • Bendotti C., Tortarolo M., Suchak S. K., Calvaresi N., Carvelli L., Bastone A., et al. Transgenic SOD1 G93A mice develop reduced GLT‐1 in spinal cord without alterations in cerebrospinal fluid glutamate levels. J Neurochem 2001; 79: 737–46
  • Guo H., Lai L., Butchbach M. E., Stockinger M. P., Shan X., Bishop G. A., et al. Increased expression of the glial glutamate transporter EAAT2 modulates excitotoxicity and delays the onset but not the outcome of ALS in mice. Hum Mol Genet 2003; 12: 2519–32
  • Gurney M. E., Cutting F. B., Zhai P., Doble A., Taylor C. P., Andrus P. K., et al. Benefit of vitamin E, riluzole, and gabapentin in a transgenic model of familial amyotrophic lateral sclerosis. Ann Neurol 1996; 39: 147–57
  • Miller R. G., Mitchell J. D., Lyon M., Moore D. H. Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Amyotroph Lateral Scler Other Motor Neuron Disord 2003; 4: 191–206
  • Poloni M., Facchetti D., Mai R., Micheli A., Agnoletti L., Francolini G., et al. Circulating levels of tumor necrosis factor‐a and its soluble receptors are increased in the blood of patients with amyotrophic lateral sclerosis. Neurosci Lett 2000; 287: 2114
  • Kawamata T., Akiyama H., Yamada T., McGeer P. L. Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. Am J Pathol 1992; 140: 691–707
  • Hall E. D., Andrus P. K., Oostveen J. A., Fleck T. J., Gurney M. E. Relationship of oxygen radical‐induced lipid peroxidative damage to disease onset and progression in a transgenic model of familial ALS. J Neurosci 1998; 53: 66–77
  • Olsen M. K., Roberds S. L., Ellerbrock B. R., Fleck T. J., McKinley D. K., Gurney M. E. Disease mechanisms revealed by transcription profiling in SOD1‐G93A transgenic mouse spinal cord. Ann Neurol 2001; 50: 730–40
  • Hensley K., Floyd R. A., Gordon B., Mou S., Pye Q. N., Stewart C., et al. Temporal patterns of cytokine and apoptosis‐related gene expression in spinal cords of the G93A‐SOD1 mouse model of amyotrophic lateral sclerosis. J Neurochem 2002; 82: 365–74
  • Yoshihara T., Ishigaki S., Yamamoto M., Liang Y., Niwa J., Takeuchi H., et al. Differential expression of inflammation‐ and apoptosis‐related genes in spinal cords of a mutant SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis. J Neurochem 2002; 80: 158–67
  • Hensley K., Fedynyshyn J., Ferrell S., Floyd R. A., Gordon B., Grammas P., et al. Message and protein‐level elevation of tumor necrosis factor a (TNFa) and TNFa‐modulating cytokines in spinal cords of the G93A‐SOD1 mouse model for amyotrophic lateral sclerosis. Neurobiol Dis 2003; 14: 74–80
  • Weydt P., Weiss M. D., Moller T., Carter G. T. Neuro‐inflammation as a therapeutic target in amyotrophic lateral sclerosis. Curr Opin Investig Drugs 2002; 3: 1720–4
  • Liu B., Jiang J. W., Wilson B., Du L., Yang S. N., Wang J. Y., et al. Systemic infusion of naloxone reduces degeneration of rat substantia nigral dopaminergic neurons induced by intranigral injection of lipopolysaccharide. J Pharmacol Exp Ther 2000; 295: 125–32
  • Liu B., Hong J. ‐S. Role of microgila in inflammation‐mediated neurodegenerative diseases; mechanisms and strategies for therapeutic intervention. J Pharmacol Exper Ther 2003; 304: 1–7
  • Liu Y., Qin L., Li G., Zhang W., An L., Liu B., et al. Dextromethorphan protects dopaminergic neurons against inflammation‐mediated degeneration through inhibition of microglial activation. J Pharmacol Exp Ther 2003; 305: 212–8
  • Kriz J., Nguyen M. D., Julien J. P. Minocycline slows disease progression in a mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 2002; 10: 268–78
  • Kriz J., Gowing G., Julien J. ‐P. Efficient three‐drug cocktail for disease induced by mutant superoxide dismutase. Annal Neurol 2003; 53: 429–36
  • van den Bosch L., Tilkin P., Lemmens G., Robberecht W. Minocycline delays disease onset and mortality in a transgenic model of ALS. Neuroreport 2002; 13: 1067–70
  • Zhang W., Narayanan M., Friedlander R. M. Additive neuroprotective effects of minocycline with creatine in a mouse model of ALS. Ann Neurol 2003; 53: 267–70
  • West M., Mhatre M., Ceballos A., Floyd R. A., Grammas P., Gabbita S. P., et al. The arachidonic acid 5‐lipoxygenase inhibitor nordihydroguaiaretic acid inhibits tumor necrosis factor a activation of microglia and extends survival of G93A‐SOD1 transgenic mice. J Neurochem 2004; 91: 133–43
  • Hirano A., Nakano I., Kurland L. T., Mulder D. W., Holley P. W., Saccomanno G. Fine structural study of neurofibrillary changes in a family with amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 1984; 43: 471–80
  • Hirano A. Cytopathology of amyotrophic lateral sclerosis. Adv Neurol 1991; 56: 91–101
  • Tomkins J., Usher P., Slade J. Y., Ince P. G., Curtis A., Bushby K., et al. Novel insertion in the KSP region of the neurofilament heavy gene in amyotrophic lateral sclerosis (ALS). Neuroreport 1998; 9: 3967–70
  • Al‐Chalabi A., Andersen P. M., Nilsson P., Chioza B., Andersson J. L., Russ C., et al. Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. Hum Mol Genet 1999; 8: 157–64
  • Bergeron C., Beric‐Maskarel K., Muntasser S., Weyer L., Somerville M. J., Percy M. E. Neurofilament light and polyadenylated mRNA levels are decreased in amyotrophic lateral sclerosis motor neurons. J Neuropathol Exp Neurol 1994; 53: 221–30
  • Williamson T. L., Bruijn L. I., Zhu Q., Anderson K. L., Anderson S. D., Julien J. P., et al. Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis‐linked superoxide dismutase 1 mutant. Proc Natl Acad Sci. USA 1998; 95: 6931–6
  • Farah C. A., Nguyen M. D., Julien J. P., Leclerc N. Altered levels and distribution of microtubule‐associated proteins before disease onset in a mouse model of amyotrophic lateral sclerosis. J Neurochem 2003; 84: 77–86
  • Corbo M., Hays A. P. Peripherin and neurofilament protein coexist in spinal spheroids of motor neuron disease. J Neuropathol Exp Neurol 1992; 51: 531–7
  • He C. Z., Hays A. P. Expression of peripherin in ubiquinated inclusions of amyotrophic lateral sclerosis. J Neurol Sci 2004; 217: 47–54
  • Gros‐Louis F., Lariviere R., Gowing G., Laurent S., Camu W., Bouchard J. P., et al. A frameshift deletion in peripherin gene associated with amyotrophic lateral sclerosis. J Biol Chem 2004; 279: 45951–6
  • Leung C. L., He C. Z., Kaufmann P., Chin S. S., Naini A., Liem R. K., et al. A pathogenic peripherin gene mutation in a patient with amyotrophic lateral sclerosis. Brain Pathol 2004; 14: 290–6
  • Beaulieu J. M., Nguyen M. D., Julien J. P. Late onset of motor neurons in mice overexpressing wild‐type peripherin. J Cell Biol 1999; 147: 531–44
  • Beaulieu J. M., Julien J. P. Peripherin‐mediated death of motor neurons rescued by overexpression of neurofilament NF‐H proteins. J Neurochem 2003; 85: 248–56
  • Williamson T. L., Cleveland D. W. Slowing of axonal transport is a very early event in the toxicity of ALS‐linked SOD1 mutants to motor neurons. Nat Neurosci 1999; 2: 50–6
  • LaMonte B. H., Wallace K. E., Holloway B. A., Shelly S. S., Ascano J., Tokito M., et al. Disruption of dynein/dynactin inhibits axonal transport in motor neurons causing late‐onset progressive degeneration. Neuron 2002; 34: 715–27
  • Wong P. C., Pardo C. A., Borchelt D. R., Lee M. K., Copeland N. G., Jenkins N. A., et al. An adverse property of a familial ALS‐linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. Neuron 1995; 14: 1105–16
  • Jaarsma D., Rognoni F., van Duijn W., Verspaget H. W., Haasdijk E. D., Holstege J. C. Cu/Zn superoxide dismutase (SOD1) accumulates in vacuolated mitochondria in transgenic mice expressing amyotrophic lateral sclerosis‐linked SOD1 mutations. Acta Neuropathol. (Berlin) 2001; 102: 293–305
  • Liu J., Lillo C., Jonsson P. A., Vande Velde C., Ward C. M., Miller T. M., et al. Toxicity of familial ALS‐linked SOD1 mutants from selective recruitment to spinal mitochondria. Neuron 2004; 43: 5–17
  • Takeuchi H., Kobayashi Y., Ishigaki S., Doyu M., Sobue G. Mitochondrial localization of mutant superoxide dismutase 1 triggers caspase‐dependent cell death in a cellular model of familial amyotrophic lateral sclerosis. J Biol Chem 2002; 277: 50966–72
  • Gunther M. R., Vangilder R., Fang J., Beattie D. S. Expression of a familial amyotrophic lateral sclerosis‐associated mutant human superoxide dismutase in yeast leads to decreased mitochondrial electron transport. Arch Biochem Biophys 2004; 431: 207–14
  • Bruijn L. I., Houseweart M. K., Kato S., Anderson K. L., Anderson S. D., Ohama E., et al. Aggregation and motor neuron toxicity of an ALS‐linked SOD1 mutant independent from wild‐type SOD1. Science 1998; 281: 1851–4
  • Wang J., Slunt H., Gonzales V., Fromholt D., Coonfield M., Copeland N. G., et al. Copper‐binding‐site‐null SOD1 causes ALS in transgenic mice: aggregates of non‐native SOD1 delineate a common feature. Hum Mol Genet 2003; 12: 2753–64
  • Son M., Cloyd C. D., Rothstein J. D., Rajendran B., Elliott J. L. Aggregate formation in Cu/Zn superoxide dismutase‐related proteins. J Biol Chem 2003; 278: 14331–6
  • Wilczak N., de Vos R. A. I., de Keyser J. Free insulin‐like growth factor (IGF)‐1 and IGF binding proteins 2, 5 and 6 in spinal motor neurons in amyotrophic lateral sclerosis. Lancet 2003; 361: 1007–11
  • Kaspar B. K., Llado J., Sherkat N., Rothstein J. D., Gage F. H. Retrograde viral delivery of IGF‐1 prolongs survival in a mouse ALS model. Science 2003; 301: 839–42
  • Acsadi G., Anguelov R. A., Yang H., Toth G., Thomas R., Jani A., et al. Increased survival and function of SOD1 mice after glial cell‐derived neurotrophic factor gene therapy. Hum Gene Ther 2002; 13: 1047–59
  • Azzouz M., Ralph G. S., Storkebaum E., Walmsley L. E., Mitrophanous K. A., Kingsman S. M., et al. VEGF delivery with retrogradely transported lentivector prolongs survival in a mouse ALS model. Nature 2004; 429: 413–7
  • Oosthuyse B., Moons L., Storkebaum E., Beck H., Nuyens D., Brusselmans K., et al. Deletion of the hypoxia‐response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat Genet 2001; 28: 131–8
  • Li M., Ona V. O., Guegan C., Chen M., Jackson‐Lewis V., Andrews L. J., et al. Functional role of caspase‐1 and caspase‐3 in an ALS transgenic mouse model. Science 2000; 288: 335–9
  • Inoue H., Tsukita K., Iwasato T., Suzuki Y., Tomioka M., Tateno M., et al. The crucial role of caspase‐9 in the disease progression of a transgenic ALS mouse model. EMBO J 2003; 22: 6665–74
  • Kostic V., Jackson‐Lewis V., de Bilbao F., Dubois‐Dauphin M., Przedborsk I. S. Bcl‐2: prolonging life in a transgenic mouse model of familial amyotrophic lateral sclerosis. Science 1997; 277: 559–62
  • Pasinelli P., Belford M. E., Lennon N., Bacskai B. J., Hyman B. T., Trotti D., et al. Amyotrophic lateral sclerosis‐associated SOD1 mutant proteins bind and aggregate with Bcl‐2 in spinal cord mitochondria. Neuron 2004; 43: 19–30
  • Sugawara T., Lewen A., Gasche Y., Yu F., Chan P. H. Overexpression of SOD1 protects vulnerable motor neurons after spinal cord injury by attenuating mitochondrial cytochrome c release. FASEB J 2002; 16: 1997–9
  • Raoul C., Estevez A. G., Nishimune H., Cleveland D. W., de Lapeyriere O., Henderson C. E., et al. Motor neuron death triggered by a specific pathway downstream of fas: potentiation by ALS‐linked SOD1 mutations. Neuron 2002; 35: 1067–83
  • Dineley K. E., Votyakova T. V., Reynolds I. J. Zinc inhibition of cellular energy production: implications for mitochondria and neurodegeneration. J Neurochem 2003; 85: 563–70
  • Wiedau‐Pazos M., Goto J. J., Rabizadeh S., Gralla E. B., Roe J. A., Lee M. K., et al. Altered reactivity of superoxide dismutase in familial amyotrophic lateral sclerosis. Science 1996; 271: 515–8
  • Estevez A. G., Crow J. P., Sampson J. B., Reiter C., Zhuang Y., Richardson G. J., et al. Induction of nitric oxide‐dependent apoptosis in motor neurons by zinc‐deficient superoxide dismutase. Science 1999; 286: 2498–5000
  • Crow J. P., Sampson J. B., Zhuang Y., Thompson J. A., Beckman J. S. Decreased zinc affinity of amyotrophic lateral sclerosis‐associated superoxide dismutase mutants leads to enhanced catalysis of tyrosine nitration by peroxynitrite. J Neurochem 1997; 69: 1936–44
  • Kang J. H., Eum W. S. Enhanced oxidative damage by the familial amyotrophic lateral sclerosis‐associated Cu/Zn‐superoxide dismutase mutants. Biochim Biophys Acta 2000; 1524: 162–70
  • Rothstein J. D. Excitotoxicity and neurodegeneration in amyotrophic lateral sclerosis. Clin Neurosci 1995; 3: 348–59
  • Becher B., Prat A., Antel J. P. Brain‐immune connection: immunoregulatory properties of CNS‐resident cells. Glia 2000; 29: 293–304
  • Allan S. M., Rothwell N. J. Cytokines and acute neurodegeneration. Nature Revs Neurosci 2001; 2: 734–44
  • Hanisch U. K. Microglia as a source and target of cytokines. Glia 2000; 40: 140–55
  • Couillard‐Despres S., Zhu Q., Wong P. C., Price D. L., Cleveland D. W., Julien J. P. Protective effect of neurofilament heavy gene overexpression in motor neuron disease induced by mutant superoxide dismutase. Proc Natl Acad Sci. USA 1998; 95: 9626–30
  • Kong J., Xu Z. Overexpression of neurofilament subunit NF‐L and NF‐H extends survival of a mouse model for amyotrophic lateral sclerosis. Neurosci Lett 2000; 281: 72–4
  • Xu Z., Cork L. C., Griffin J. W., Cleveland D. W. Increased expression of neurofilament subunit NF‐L produces morphological alterations that resemble the pathology of human motor neuron disease. Cell 1993; 73: 23–33
  • Meier J., Couillard‐Despres S., Jacomy H., Gravel C., Julien J. P. Extra neurofilament NF‐L subunits rescue motor neuron disease caused by overexpression of the human NF‐H gene in mice. J Neuropathol Exp Neurol 1999; 58: 1099–1100
  • Kieran D., Hafezparast M., Bohnert S., Dick J. R. T., Martin J., Schiavo G., et al. A mutation in dynein rescues axonal transport defects and extends the life span of ALS mice. J Cell Biol 2005; 169: 561–7
  • Kabashi E., Agar J. N., Taylor D. M., Minotti S., Durham H. D. Focal dysfunction of the proteasome: a pathogenic factor in a mouse model of amyotrophic lateral sclerosis. J Neurochem 2004; 89: 1325–35
  • Bruening W., Roy J., Giasson B., Figlewicz D. A., Mushynski W. E., Durham H. D. Up‐regulation of protein chaperones preserves viability of cells expressing toxic Cu/Zn‐superoxide dismutase mutants associated with amyotrophic lateral sclerosis. J Neurochem 1999; 72: 693–9
  • Lai E. C., Felice K. J., Festoff B. W., Gawel M. J., Gelinas D. F., Kratz R., et al. Effect of recombinant human insulin‐like growth factor‐1 on progression of ALS: a placebo‐controlled study. Neurology 1997; 49: 1621–30
  • Borasio G. D., Robberecht W., Leigh P. N., Emile J., Guiloff R. J., Jerusalem F., et al. A placebo‐controlled trial of human insulin‐like growth factor‐1 on amyotrophic lateral sclerosis. Neurology 1998; 51: 583–6
  • Zoratti M., Szabo I. The mitochondrial permeability transition. Biochim Biophys Acta 1995; 1241: 139–76
  • Jiang D., Sullivan P. G., Sensi S. L., Steward O., Weiss J. H. Zn(2+) induces permeability transition pore opening and release of pro‐apoptotic peptides from neuronal mitochondria. J Biol Chem 2001; 276: 47524–9
  • Volterra A., Trotti D., Tromba C., Floridi S., Racagni G. Glutamate uptake inhibition by oxygen free radicals in rat cortical astrocytes. J Neurosci 1994; 14: 2924–32
  • Christman J. W., Blackwell T. S., Juurlink B. H. J. Redox regulation of nuclear factor kappa B: therapeutic potential for attenuating inflammatory responses. Brain Pathol 2000; 10: 153–62
  • Buttket T. M., Sandstom P. A. Oxidative stress as a mediator of apoptosis. Immunol Today 1994; 15: 7–10
  • Colavitti R., Pani G., Bedogni B., Anzevino R., Borrello S., Waltenberger J., et al. Reactive oxygen species as downstream mediators of angiogenic signaling by vascular endothelial growth factor receptor‐2/KDR. J Biol Chem 2002; 277: 3101–8
  • Finkel T. Oxygen radicals and signaling. Curr Opin Cell Biol 1998; 10: 248–53
  • Cassina P., Pehar M., Vargas M. R., Castellanos R., Barbeito A. G., Estevez A. G., et al. Astrocyte activation by fibroblast growth factor‐1 and motor neuron apoptosis: implications for amyotrophic lateral sclerosis. J Neurochem 2005; 93: 38–46
  • Kim N. H., Kang J. H. Oxidative modification of neurofilament‐L by copper‐catalyzed reaction. J Biochem Mol Biol 2003; 36: 488–92
  • Lafon‐Cazal M., Pietri S., Culcasi M., Bockaert J. NMDA‐dependent superoxide production and neurotoxicity. Nature 1993; 364: 535–7
  • Kreutzberg G. W. Microglia: a sensor for pathological events in the CNS. Trends Neurosci 1996; 19: 312–8
  • Ankarcrona M., Dypbukt J. M., Bonfoco E., Zhivotovsky B., Orrenius S., Lipton S. A., et al. Glutamate‐induced neuronal death: a succession of necrosis or apoptosis depending on mitochondrial function. Neuron 1995; 15: 961–73
  • Chung R. S., McCormack G. H., King A. E., West A. K., Vickers J. C. Glutamate induces rapid loss of axonal neurofilament proteins from cortical neurons in vitro. Exp Neurol 1995; 193: 481–8
  • Tarabal O., Caldero J., Casas C., Oppenheim R. W., Esquerda J. E. Protein retention in the endoplasmic reticulum, blockade of programmed cell death and autophagy selectively occur in spinal cord motor neurons after glutamate receptor‐mediated injury. Mol Cell Neurosci 2005; 29: 283–98
  • Choi J. S., Kim S. Y., Park H. J., Cha J. H., Choi Y. S., Chung J. W., et al. Differential regulation of ciliary neurotrophic factor and its receptor in the rat hippocampus in response to kainic acid‐induced excitotoxicity. Mol Cells 2004; 17: 292–6
  • Colton C. A., Snell J., Chernyshev O., Gilbert D. L. Induction of superoxide anion and nitric oxide production in cultured microglia. Ann N.Y. Acad Sci 1994; 738: 54–63
  • Tikka T., Fiebich B. L., Goldsteins G., Keinanen R., Koistinaho J. Minocycline, a tetracycline derivative, is neuroprotective against excitotoxicity by inhibiting activation and proliferation of microglia. J Neurosci 2001; 21: 2580–8
  • Turpaev K., Litvinov D., Dubovaya V., Panasyuk A., Ivanov D., Prassolov V. Induction of vascular endothelial growth factor by nitric oxide in cultured human articular chondrocytes. Biochimie 2001; 83: 515–22
  • Rempel H., Kusdra L., Pulliam L. Interleukin‐1b up‐regulates expression of neurofilament light in human neuronal cells. J Neurochem 2001; 78: 640–5
  • Emerit J., Edeas M., Bricaire F. Neurodegenerative diseases and oxidative stress. Biomed Pharmacother 2004; 58: 39–46
  • Grzenkowicz‐Wydra J., Cisowski J., Nakonieczna J., Zarebski A., Udilova N., Nohl H., et al. Gene transfer of Cu/Zn superoxide dismutase enhances the synthesis of vascular endothelial growth factor. Mol Cell Biochem 2004; 264: 169–81
  • Escartin C., Boyer F., Bemelmans A. P., Hantraye P., Brouillet E. Insulin growth factor‐1 protects against excitotoxicity in the rat striatum. Neuroreport 2004; 15: 2251–4
  • Schuettauf F., Vorwerk C., Naskar R., Orlin A., Quinto K., Zurakowski D., et al. Adeno‐associated viruses containing bFGF or BDNF are neuroprotective against excitotoxicity. Curr Eye Res 2004; 29: 379–86
  • Tseng H. C., Dichter M. A. Platelet‐derived growth factor‐BB pretreatment attenuates excitotoxic death in cultured hippocampal neurons. Neurobiol Dis 2005; 19: 77–83
  • Kitagawa A., Nakayama T., Takenaga M., Matsumoto K., Tokura Y., Ohta Y., et al. Lecithinized brain‐derived neurotrophic factor promotes the differentiation of embryonic stem cells in vitro and in vivo. Biochem Biophys Res Commun 2005; 328: 1051–7
  • Borchelt D. R., Guarnieri M., Wong P. C., Lee M. K., Slunt H. S., Xu Z. S., et al. Superoxide dismutase 1 subunits with mutations linked to familial amyotrophic lateral sclerosis do not affect wild‐type subunit function. J Biol Chem 1995; 270: 3234–8
  • Reaume A. G., Elliott J. L., Hoffman E. K., Kowall N. W., Ferrante R. J., Siwek D. F., et al. Motor neurons in Cu/Zn superoxide dismutase‐deficient mice develop normally but exhibit enhanced cell death after axonal injury. Nat Genet 1996; 13: 43–7
  • Bruijn L. I., Cleveland D. W. Unravelling the mechanisms involved in motor neuron degeneration in ALS. Annu Rev Neurosci 2004; 27: 723–49
  • Bruijn L. I., Beal M. F., Becher M. W., Schulz J. B., Wong P. C., Price D. L., et al. Elevated free nitrotyrosine levels, but not protein‐bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)‐like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS‐linked superoxide dismutase 1 mutant. Proc Natl Acad Sci. USA 1997; 94: 7606–11
  • Forman H. J., Fridovich I. On the stability of bovine superoxide dismutase. The effects of metals. J Biol Chem 1973; 248: 2645–9
  • Goto J. J., Zhu H., Sanchez R. J., Nersissian A., Gralla E. B., Valentine J. S., et al. Loss of in vitro metal ion binding specificity in mutant copper‐zinc superoxide dismutases associated with familial amyotrophic lateral sclerosis. J Biol Chem 2000; 275: 1007–14
  • Subramaniam J. R., Lyons W. E., Liu J., Bartnikas T. B., Rothstein J. D., Price D. L., et al. Mutant SOD1 causes motor neuron disease independent of copper chaperone‐mediated copper loading. Nat Neurosci 2002; 5: 301–7
  • Elliott J. L. Zinc and copper in the pathogenesis of amyotrophic lateral sclerosis. Prog Neuro‐Psychopharmacol & Biol Psychiat 2001; 25: 1169–85
  • Lyons T. J., Liu H., Goto J. J., Nersissian A., Roe J. A., Graden J. A., et al. Mutations in copper‐zinc superoxide dismutase that cause amyotrophic lateral sclerosis alter the zinc binding site and the redox behavior of the protein. Proc Natl Acad Sci. USA 1996; 93: 12240–4
  • Rodriguez J. A., Valentine J. S., Eggers D. K., Roe J. A., Tiwari A., Brown R. H Jr., et al. Familial amyotrophic lateral sclerosis‐associated mutations decrease the thermal stability of distinctly metallated species of human copper/zinc superoxide dismutase. J Biol Chem 2002; 277: 15932–7
  • Williamson T. L., Corson L. B., Huang L., Burlingame M., Liu J., Bruijn L. I., et al. Toxicity of ALS‐linked SOD1 mutants. Science 2000; 286: 2498–500
  • Noh K. M., Kim Y. H., Koh J. Y. Mediation by membrane protein kinase C of zinc‐induced oxidative neuronal injury in mouse cortical cultures. J Neurochem 1999; 72: 1609–16
  • Persechini A., McMillan K., Masters B. S. Inhibition of nitric oxide synthase activity by Zn2+ ion. Biochemistry 1995; 34: 15091–5
  • Oteiza P. I., Olin K. L., Fraga C. G., Keen C. L. Zinc deficiency causes oxidative damage to proteins, lipids and DNA in rat testes. J Nutr 1995; 125: 823–9
  • Bray T. M., Bettger W. J. The physiological role of zinc as an antioxidant. Free Radic Biol Med 1990; 8: 281–91
  • Chen N., Moshaver A., Raymond L. A. Differential sensitivity of recombinant N‐methyl‐D‐aspartate receptor subtypes to zinc inhibition. Mol Pharmacol 1997; 51: 1015–23
  • Sensi S. L., Jeng J. M. Re‐thinking the excitotoxic ionic milieu: the emerging role of zinc in ischemic neuronal injury. Curr Mol Med 2004; 4: 83–107
  • Westbrook G. L., Mayer M. L. Micromolar concentrations of Zn2+ antagonize NMDA and GABA responses of hippocampal neurons. Nature 1987; 328: 640–3
  • Harrison N. L., Radke H. K., Talukder G., French‐Mullen J. M. Zinc modulates transient outward current gating in hippocampal neurons. Receptors Channels 1993; 1: 153–63
  • Raman C. S., Li H., Martasek P., Kral V., Masters B. S., Poulos T. L. Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center. Cell 1998; 95: 939–50
  • Ghosh D. K., Crane B. R., Ghosh S., Wolan D., Gachhui R., Crooks C., et al. Inducible nitric oxide synthase: role of the N‐terminal beta‐hairpin hook and pterin‐binding segment in dimerization and tetrahydrobiopterin interaction. EMBO J 1999; 18: 6260–70
  • Ge W. W., Wen W., Strong W., Leystra‐Lantz C., Strong M. J. Mutant copper‐zinc superoxide dismutase binds to and destabilizes human low molecular weight neurofilament mRNA. J Biol Chem 2005; 280: 118–24
  • Lorusso M., Cocco T., Sardanelli A. M., Minuto M., Bonomi F., Papa S. Interaction of Zn2+ with the bovine‐heart mitochondrial bc1 complex. Eur J Biochem 1991; 197: 555–61
  • Brown A. M., Kristal B. S., Effron M. S., Shestopalov A. I., Ullucci P. A., Sheu K. F., et al. Zn2+ inhibits alpha‐ketoglutarate‐stimulated mitochondrial respiration and the isolated alpha‐ketoglutarate dehydrogenase complex. J Biol Chem 2000; 275: 13441–7
  • Maret W., Yetman C. A., Jiang L. Enzyme regulation by reversible zinc inhibition: glycerol phosphate dehydrogenase as an example. Chem Biol Interact 2001; 130–132: 891–901
  • Gazaryan I. G., Krasnikov B. F., Ashby G. A., Thorneley R. N., Kristal B. S., Brown A. M. Zinc is a potent inhibitor of thiol oxidoreductase activity and stimulates reactive oxygen species production by lipoamide dehydrogenase. J Biol Chem 2002; 277: 10064–72
  • Rakhit R., Cunningham P., Furtos‐Matei A., Dahan S., Qi X. F., Crow J. P., et al. Oxidation‐induced misfolding and aggregation of superoxide dismutase and its implications for amyotrophic lateral sclerosis. J Biol Chem 2002; 277: 47551–6
  • Sampson J. B., Beckman J. S. Hydrogen peroxide damages the zinc‐binding site of zinc‐deficient Cu/Zn superoxide dismutase. Arch Biochem Biophys 2001; 392: 8–13
  • Curtain C. C., Ali F., Volitakis I., Cherny R. A., Norton R. S., Beyreuther K., et al. Alzheimer's disease amyloid‐beta binds copper and zinc to generate an allosterically ordered membrane‐penetrating structure containing superoxide dismutase‐like subunits. J Biol Chem 2001; 276: 20466–73
  • Quaglio E., Chiesa R., Harris D. A. Copper converts the cellular prion protein into a protease‐resistant species that is distinct from the scrapie isoform. J Biol Chem 2001; 276: 11432–8
  • Yu Z. P., Le G. W., Shi Y. H. Effect of zinc sulphate and zinc methionine on growth, plasma growth hormone concentration, growth hormone receptor and insulin‐like growth factor‐1 gene expression in mice. Clin Exp Pharmacol Physiol 2005; 32: 273–8
  • Kwon H. S., Shin H. C., Kim J. S. Suppression of vascular endothelial growth factor expression at the transcriptional and post‐transcriptional levels. Nucleic Acids Res 2005; 33: 74
  • Ciais D., Cherradi N., Bailly S., Grenier E., Berra E., Pouyssegur J., et al. Destabilization of vascular endothelial growth factor mRNA by the zinc‐finger protein TIS11b. Oncogene 2004; 23: 8673–80
  • Kuramoto K., Uesaka T., Kimura A., Kobayashi M. H. W., Katoh O. ZK7, a novel zinc finger gene, is induced by vascular endothelial growth factor and inhibits apoptotic death in hematopoietic cells. Cancer Res 2000; 60: 425–30
  • Woodbury D., Schaar D. G., Ramakrishnan L., Black I. B. Novel structure of the human GDNF gene. Brain Res 1998; 803: 95–104
  • Yajima S., Lammers C. H., Lee S. H., Hara Y., Mizuno K., Mouradian M. M. Cloning and characterization of murine glial cell‐derived neurotrophic factor inducible transcription factor (MGIF). J Neurosci 1997; 17: 8657–66
  • Uzzo R. G., Leavis P., Hatch W., Gabai V. L., Dulin N., Zvartau N., et al. Zinc inhibits nuclear factor‐kappa B activation and sensitizes prostate cancer cells to cytotoxic agents. Clin Cancer Res 2002; 8: 3579–83
  • Schott‐Ohly P., Lgssiar A., Partke H. J., Hassan M., Friesen N., Gleichmann H. Prevention of spontaneous and experimentally induced diabetes in mice with zinc sulfate‐enriched drinking water is associated with activation and reduction of NF‐kappa B and AP‐1 in islets, respectively. Exp Biol Med. (Maywood) 2004; 229: 1177–85
  • Maire M. A., Rast C., Pagnout C., Vasseu R. P. Changes in expression of bcl‐2 and bax in Syrian hamster embryo (SHE) cells exposed to ZnCl(2). Arch Toxicol 2004; 79: 90–101
  • Iitaka M., Kakinuma S., Fujimaki S., Oosuga I., Fujita T., Yamanaka K., et al. Induction of apoptosis and necrosis by zinc in human thyroid cancer cell lines. J Endocrinol 2001; 169: 417–24
  • Hainaut P., Mann K. Zinc binding and redox control of p53 structure and function. Antioxid Redox Signal 2001; 3: 611–23
  • Frederickson C. J., Suh S. W., Silva D., Frederickson C. J., Thompson R. B. Importance of zinc in the central nervous system: the zinc‐containing neuron. J Nutr 2000; 130: S147–183
  • Hidalgo J., Aschner M., Zatta P., Vasak M. Roles of the metallothionein family of proteins in the central nervous system. Brain Res Bull 2001; 55: 133–45
  • Vela J. M., Hidalgo J., Gonzalez B., Castellano B. Induction of metallothionein in astrocytes and microglia in the spinal cord from the myelin‐deficient jimpy mouse. Brain Res 1997; 767: 345–55
  • Acarin L., Gonzalez B., Hidalgo J., Castro A. J., Castellano B. Primary cortical glial reaction versus secondary thalamic glial response in the excitotoxically injured young brain: astroglial response and metallothionein expression. Neuroscience 1999; 92: 827–39
  • Carrasco J., Giralt M., Molinero A., Penkowa M., Moos T., Hidalgo J. Metallothionein (MT)‐III: generation of polyclonal antibodies, comparison with MT‐I+II in the freeze lesioned rat brain and in a bioassay with astrocytes, and analysis of Alzheimer's disease brains. J Neurotrauma 1999; 16: 1115–29
  • Carrasco J., Penkowa M., Hadberg H., Molinero A., Hidalgo J. Enhanced seizures and hippocampal neurodegeneration following kainic acid‐induced seizures in metallothionein‐I+II‐deficient mice. Eur J Neurosci 2000a; 12: 2311–22
  • Carrasco J., Giralt M., Penkowa M., Stalder A. K., Campbell I. L., Hidalgo J. Metallothioneins are up‐regulated in symptomatic mice with astrocyte‐targeted expression of tumor necrosis factor‐alpha. Exp Neurol 2000b; 163: 46–54
  • Hamer D. H. Metallothionein. Annu Rev Biochem 1986; 55: 913–51
  • Hager I. J., Palmiter R. D. Transcriptional regulation of mouse liver metallothionein‐I gene by glucocorticoids. Nature 1981; 291: 340–2
  • Hozumi I., Inuzuka T., Hiraiwa M., Uchida Y., Anezaki T., Ishiguro H., et al. Changes of growth inhibitory factor after stab wounds in rat brain. Brain Res 1995; 688: 143–8
  • Dalton T., Pazdernik T. L., Wagner J., Samson F., Andrews G. K. Temporospatial patterns of expression of metallothionein‐I and III and other stress‐related genes in brain after kainic acid‐induced seizures. Neurochem Int 1995; 27: 59–71
  • Penkowa M., Moos T. Disruption of the blood‐brain interface in neonatal rat neocortex induces a transient expression of metallothionein in reactive astrocytes. Glia 1995; 13: 217–27
  • Kim E. H., Kim T. S., Sun W., Kim D. S., Chung H. S., Kim D. K., et al. Differential regulation of metallothionein‐I and metallothionein‐II mRNA expression in the rat brain following traumatic brain injury. Mol Cells 2004; 18: 326–31
  • Penkowa M., Giralt M., Thomsen P. S., Carrasco J., Hidalgo J. Zinc or copper deficiency‐induced impaired inflammatory response to brain trauma may be caused by the concomitant metallothionein changes. J Neurotrauma 2001; 18: 447–63
  • Erickson J. C., Hollopeter G., Thomas S. A., Froelick G. J., Palmiter R. D. Disruption of the metallothionein‐III gene in mice: analysis of brain zinc, behavior, and neuron vulnerability to metals, aging, and seizures. J Neurosci 1997; 17: 1271–81
  • Cole T. B., Robbins C. A., Wenzel H. J., Schwartzkroin P. A., Palmiter R. D. Seizures and neuronal damage in mice lacking vesicular zinc. Epilepsy Res 2000; 39: 153–69
  • Gong Y. H., Elliott J. L. Metallothionein expression is altered in a transgenic murine model of familial amyotrophic lateral sclerosis. Exp Neurol 2000; 162: 27–36
  • Ignacio S., Moore D. H., Smith A. P., Lee N. M. Effect of neuroprotective drugs on gene expression in G93A/SOD1 mice. Ann NY Acad Sci 2005; 1053: 121–36
  • Nagano S., Satoh M., Sumi H., Fujimura H., Tohyama C., Yanagihara T., et al. Reduction of metallothioneins promotes the disease expression of familial amyotrophic lateral sclerosis mice in a dose‐dependent manner. Eur J Neurosci 2001; 13: 1363–70
  • Puttaparthi K., Gitomer W. L., Krishnan U., Son M., Rajendran B., Elliott J. L. Disease progression in a transgenic model of familial amyotrophic lateral sclerosis is dependent on both neuronal and non‐neuronal zinc‐binding proteins. J Neurosci 2002; 22: 8790–6
  • Sillevis Smitt P. A., Blaauwgeers H. G., Troost D., de Jong J. M. Metallothionein immunoreactivity is increased in the spinal cord of patients with amyotrophic lateral sclerosis. Neurosci Lett 1992; 144: 107–10
  • Blaauwgeers H. G., Anwar Chand M., van den Berg F. M., Vianney de Jong J. M., Troost D. Expression of different metallothionein messenger ribonucleic acids in motor cortex, spinal cord and liver from patients with amyotrophic lateral sclerosis. J Neurol Sci 1996; 142: 39–44
  • Liuzzi J. P., Cousins R. P. Mammalian zinc transporters. Annu Rev Nutr 2004; 24: 151–72
  • Sekler I., Moran A., Hershfinkel M., Dori A., Margulis A., Birenzweig N., et al. Distribution of the zinc transporter ZnT‐1 compared with chelatable zinc in the mouse brain. J Comp Neurol 2002; 447: 201–9
  • Wenzel H. J., Cole T. B., Born D. E., Schwartzkroin P. A., Palmiter R. D. Ultrastructural localization of zinc transporter‐3 (ZnT‐3) to synaptic vesicle membranes within mossy fiber boutons in the hippocampus of mouse and monkey. Proc Natl Acad Sci. USA 1997; 94: 12676–81
  • Nolte C., Gore A., Sekler I., Kresse W., Hershfinkel M., Hoffmann A., et al. ZnT‐1 expression in astroglial cells protects against zinc toxicity and slows the accumulation of intracellular zinc. Glia 2004; 148: 145–55
  • Segal D., Ohana E., Besser L., Hershfinkel M., Moran A., Sekler I. A role for ZnT‐1 in regulating cellular cation influx. Biochem Biophys Res Commun 2004; 323: 1145–50
  • Devergnas S., Chimienti F., Naud N., Pennequin A., Coquerel Y., Chantegrel J., et al. Differential regulation of zinc efflux transporters ZnT‐1, ZnT‐5 and ZnT‐7 gene expression by zinc levels: a real time RT‐PCR study. Biochem Pharmacol 2004; 68: 699–709
  • Wang F., Dufner‐Beattie J., Kim B. E., Petris M. J., Andrews G. K., Eide D. J. Zinc‐stimulated endocytosis controls activity of the mouse Zip1 and Zip3 zinc uptake transporters. J Biol Chem 2004; 279: 24631–9
  • Lovell M. A., Smith J. L., Xiong S., Markesbery W. R. Alterations in zinc transporter protein‐1 (ZnT‐1) in the brain of subjects with mild cognitive impairment, early, and late‐stage Alzheimer's disease. Neurotox Res. 2005; 7: 265–71
  • Friedlich A. L., Lee J. ‐Y., van Groen T., Cherny R. A., Volitakis I., Cole T. B., et al. Neuronal zinc exchange with the blood vessel wall promotes cerebral amyloid angiopathy in an animal model of Alzheimer's disease. J Neurosci 2004; 24: 3453–9
  • Varshney U., Hoar D. I., Starozik D., Gedamu L. A frequent restriction fragment length polymorphism in the human metallothionein‐II processed gene region is evolutionarily conserved. Mol Biol Med 1984; 2: 193–206
  • Morahan J. M., Yu B., Trent R. J., Pamphlett R. Screening the metallothionein III gene in sporadic amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2005; 6: 115–7
  • Cragg R. A., Christie G. R., Phillips S. R., Russi R. M., Kury S., Mathers J. C., et al. A novel zinc‐regulated human zinc transporter, hZTL1, is localized to the enterocyte Ap6cal membrane. J Biol Chem 2002; 277: 22789–97
  • Nishimura A. L., Mitne‐Neto M., Silva H. C., Richieri‐Costa A., Middleton S., Cascio D., et al. A mutation in the vesicle‐trafficking protein VAPB causes late‐onset spinal muscular atrophy and amyotrophic lateral sclerosis. Am J Hum Genet 2004; 75: 822–31
  • Cox P. A., Banack S. A., Murch S. J. Biomagnification of cyanobacterial neurotoxins and neurodegenerative disease among the Chamorro people of Guam. Proc Natl Acad Sci. USA 2003; 100: 13380–3
  • Armon C. Excess incidence of ALS in young Gulf War veterans. Neurology 2004; 63: 1986–7

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.