Oxidative stress in neurodegeneration: cause or consequence? (original) (raw)

• Hensley, K. et al. Electrochemical analysis of protein nitrotyrosine and dityrosine in the Alzheimer brain indicates region-specific accumulation. J. Neurosci. 18, 8126–8132 (1998).
  Article CAS PubMed Google Scholar
• Butterfield, D.A., Castegna, A., Lauderback, C.M. & Drake, J. Evidence that amyloid β-peptide-induced lipid peroxidation and its sequelae in Alzheimer's disease brain contribute to neuronal death. Neurobiol. Aging 23, 655–664 (2002).
  Article PubMed Google Scholar
• Dexter, D.T. et al. Basal lipid peroxidation in substantia nigra is increased in Parkinson's disease. J. Neurochem. 52, 381–389 (1989).
  Article CAS PubMed Google Scholar
• Pedersen, W.A. et al. Protein modification by the lipid peroxidation product 4-hydroxynonenal in the spinal cords of amyotrophic lateral sclerosis patients. Ann. Neurol. 44, 819–824 (1998).
  Article CAS PubMed Google Scholar
• Beal, M.F. et al. Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis. Ann. Neurol. 42, 644–654 (1997).
  Article CAS PubMed Google Scholar
• Smith, M.A., Richey Harris, P.L., Sayre, L.M., Beckman, J.S. & Perry, G. Widespread peroxynitrite-mediated damage in Alzheimer's disease. J. Neurosci. 17, 2653–2657 (1997).
  Article CAS PubMed Google Scholar
• Good, P.F., Hsu, A., Werner, P., Perl, D.P. & Olanow, C.W. Protein nitration in Parkinson's disease. J. Neuropathol. Exp. Neurol. 57, 338–342 (1998).
  Article CAS PubMed Google Scholar
• Aoyama, K. et al. Nitration of manganese superoxide dismutase in cerebrospinal fluids is a marker for peroxynitrite-mediated oxidative stress in neurodegenerative diseases. Ann. Neurol. 47, 524–527 (2000).
  Article CAS PubMed Google Scholar
• Giasson, B.I. et al. Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions. Science 290, 985–989 (2000).
  Article CAS PubMed Google Scholar
• Giasson, B.I. et al. A panel of epitope-specific antibodies detects protein domains distributed throughout human α-synuclein in Lewy bodies of Parkinson's disease. J. Neurosci. Res. 59, 528–533 (2000).
  Article CAS PubMed Google Scholar
• Horiguchi, T. et al. Nitration of tau protein is linked to neurodegeneration in tauopathies. Am. J. Pathol. 163, 1021–1031 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Zemlan, F.P., Thienhaus, O.J. & Bosmann, H.B. Superoxide dismutase activity in Alzheimer's disease: possible mechanism for paired helical filament formation. Brain Res. 476, 160–162 (1989).
  Article CAS PubMed Google Scholar
• Pappolla, M.A., Omar, R.A., Kim, K.S. & Robakis, N.K. Immunohistochemical evidence of oxidative stress in Alzheimer's disease. Am. J. Pathol. 140, 621–628 (1992).
  CAS PubMed PubMed Central Google Scholar
• Gabbita, S.P., Aksenov, M.Y., Lovell, M.A. & Markesbery, W.R. Decrease in peptide methionine sulfoxide reductase in Alzheimer's disease brain. J. Neurochem. 73, 1660–1666 (1999).
  Article CAS PubMed Google Scholar
• Perry, T.L., Godin, D.V. & Hansen, S. Parkinson's disease: a disorder due to nigral glutathione deficiency? Neurosci. Lett. 33, 305–310 (1982).
  Article CAS PubMed Google Scholar
• Perry, TL. & Yong, V.W. Idiopathic Parkinson's disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra of patients. Neurosci. Lett. 67, 269–274 (1986).
  Article CAS PubMed Google Scholar
• Pearce, R.K., Owen, A., Daniel, S., Jenner, P. & Marsden, C.D. Alterations in the distribution of glutathione in the substantia nigra in Parkinson's disease. J. Neural Transm. 104, 661–677 (1997).
  Article CAS PubMed Google Scholar
• Riederer, P. et al. Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J. Neurochem. 52, 515–520 (1989).
  Article CAS PubMed Google Scholar
• Sofic, E., Paulus, W., Jellinger, K., Riederer, P. & Youdim, M.B. Selective increase of iron in substantia nigra zona compacta of parkinsonian brains. J. Neurochem. 56, 978–982 (1991).
  Article CAS PubMed Google Scholar
• Jellinger, K.A. et al. Iron and ferritin in substantia nigra in Parkinson's disease. Adv. Neurol. 60, 267–272 (1993).
  CAS PubMed Google Scholar
• Cudkowicz, M.E. et al. Epidemiology of mutations in superoxide dismutase in amyotrophic lateral sclerosis. Ann. Neurol. 41, 210–221 (1997).
  Article CAS PubMed Google Scholar
• Gurney, M.E. et al. Motor neuron degeneration in mice that express a human Cu,Zn superoxide dismutase mutation. Science 264, 1772–1775 (1994).
  Article CAS PubMed Google Scholar
• 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. Res. 53, 66–77 (1998).
  Article CAS PubMed Google Scholar
• Warita, H., Hayashi, T., Murakami, T., Manabe, Y. & Abe, K. Oxidative damage to mitochondrial DNA in spinal motoneurons of transgenic ALS mice. Brain Res. Mol. Brain Res. 89, 147–152 (2001).
  Article CAS PubMed Google Scholar
• Dal Canto, M.C. Comparison of pathological alterations in ALS and a murine transgenic model: pathogenetic implications. Clin. Neurosci. 3, 332–337 (1995).
  PubMed Google Scholar
• Zhang, J., Graham, D.G., Montine, T.J. & Ho, Y.S. Enhanced _N_-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice deficient in CuZn-superoxide dismutase or glutathione peroxidase. J. Neuropathol. Exp. Neurol. 59, 53–61 (2000).
  Article CAS PubMed Google Scholar
• Klivenyi, P. et al. Mice deficient in cellular glutathione peroxidase show increased vulnerability to malonate, 3-nitropropionic acid, and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine. J. Neurosci. 20, 1–7 (2000).
  Article CAS PubMed Google Scholar
• Przedborski, S. et al. Transgenic mice with increased Cu/Zn-superoxide dismutase activity are resistant to _N_-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity. J. Neurosci. 12, 1658–1667 (1992).
  Article CAS PubMed Google Scholar
• Andreassen, O.A. et al. Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP. Exp. Neurol. 167, 189–195 (2001).
  Article CAS PubMed Google Scholar
• Klivenyi, P. et al. Manganese superoxide dismutase overexpression attenuates MPTP toxicity. Neurobiol. Dis. 5, 253–258 (1998).
  Article CAS PubMed Google Scholar
• Klivenyi, P. et al. Inhibition of neuronal nitric oxide synthase protects against MPTP toxicity. Neuroreport 11, 1265–1268 (2000).
  Article CAS PubMed Google Scholar
• Liberatore, G.T. et al. Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat. Med. 5, 1403–1409 (1999).
  Article CAS PubMed Google Scholar
• Dehmer, T., Lindenau, J., Haid, S., Dichgans, J. & Schulz, J.B. Deficiency of inducible nitric oxide synthase protects against MPTP toxicity in vivo. J. Neurochem. 74, 2213–2216 (2000).
  Article CAS PubMed Google Scholar
• Itzhak, Y., Martin, J.L. & Ali, S.F. Methamphetamine- and 1-methyl-4-phenyl- 1,2,3, 6-tetrahydropyridine-induced dopaminergic neurotoxicity in inducible nitric oxide synthase–deficient mice. Synapse 34, 305–312 (1999).
  Article CAS PubMed Google Scholar
• Zhu, S. et al. Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice. Nature 417, 74–78 (2002).
  Article CAS PubMed Google Scholar
• Wu, D.C. et al. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J. Neurosci. 22, 1763–1771 (2002).
  Article CAS PubMed Google Scholar
• Du, Y. et al. Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease. Proc. Natl. Acad. Sci. USA 98, 14669–14674 (2001).
  Article CAS PubMed Google Scholar
• Yang, L. et al. Minocycline enhances MPTP toxicity to dopaminergic neurons. J. Neurosci. Res. 74, 278–285 (2003).
  Article CAS PubMed Google Scholar
• Sano, M. et al. A controlled trial of selegiline, α-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N. Engl. J. Med. 336, 1216–1222 (1997).
  Article CAS PubMed Google Scholar
• Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. The Parkinson Study Group. N. Engl. J. Med. 328, 176–183 (1993).
• Desnuelle, C., Dib, M., Garrel, C. & Favier, A. A double-blind, placebo-controlled randomized clinical trial of α-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole-tocopherol Study Group. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 2, 9–18 (2001).
  Article CAS PubMed Google Scholar
• Gurney, M.E., Fleck, T.J., Himes, C.S. & Hall, E.D. Riluzole preserves motor function in a transgenic model of familial amyotrophic lateral sclerosis. Neurology 50, 62–66 (1998).
  Article CAS PubMed Google Scholar
• Gurney, M.E. et al. Benefit of vitamin E, riluzole, and gabapentin in a transgenic model of familial amyotrophic lateral sclerosis. Ann. Neurol. 39, 147–157 (1996).
  Article CAS PubMed Google Scholar
• Kieran, D. et al. Treatment with arimoclomol, a coinducer of heat shock proteins, delays disease progression in ALS mice. Nat. Med. 10, 402–405 (2004).
  Article CAS PubMed Google Scholar
• Winklhofer, K.F., Henn, I.H., Kay-Jackson, P.C., Heller, U. & Tatzelt, J. Inactivation of parkin by oxidative stress and C-terminal truncations: a protective role of molecular chaperones. J. Biol. Chem. 278, 47199–47208 (2003).
  Article CAS PubMed Google Scholar
• Bruening, W. et al. Up-regulation of protein chaperones preserves viability of cells expressing toxic Cu/Zn-superoxide dismutase mutants associated with amyotrophic lateral sclerosis. J. Neurochem. 72, 693–699 (1999).
  Article CAS PubMed Google Scholar
• Takeuchi, H. et al. Hsp70 and Hsp40 improve neurite outgrowth and suppress intracytoplasmic aggregate formation in cultured neuronal cells expressing mutant SOD1. Brain Res. 949, 11–22 (2002).
  Article CAS PubMed Google Scholar
• Warrick, J.M. et al. Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nat. Genet. 23, 425–428 (1999).
  Article CAS PubMed Google Scholar
• Manning-Bog, A.B., McCormack, A.L., Purisai, M.G., Bolin, L.M. & Di Monte, D.A. α-Synuclein overexpression protects against paraquat-induced neurodegeneration. J. Neurosci. 23, 3095–3099 (2003).
  Article CAS PubMed Google Scholar
• Conway, K.A., Rochet, J.C., Bieganski, R.M. & Lansbury, P.T., Jr. Kinetic stabilization of the α-synuclein protofibril by a dopamine–α-synuclein adduct. Science 294, 1346–1349 (2001).
  Article CAS PubMed Google Scholar
• Volles, M.J. & Lansbury, P.T., Jr. Vesicle permeabilization by protofibrillar α-synuclein is sensitive to Parkinson's disease-linked mutations and occurs by a pore-like mechanism. Biochemistry 41, 4595–4602 (2002).
  Article CAS PubMed Google Scholar
• Lotharius, J. & Brundin, P. Impaired dopamine storage resulting from α-synuclein mutations may contribute to the pathogenesis of Parkinson's disease. Hum. Mol. Genet. 11, 2395–2407 (2002).
  Article CAS PubMed Google Scholar
• Xu, J. et al. Dopamine-dependent neurotoxicity of α-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat. Med. 8, 600–606 (2002).
  Article CAS PubMed Google Scholar
• Abeliovich, A. et al. Mice lacking α-synuclein display functional deficits in the nigrostriatal dopamine system. Neuron 25, 239–252 (2000).
  Article CAS PubMed Google Scholar
• Jha, N., Kumar, M.J., Boonplueang, R. & Andersen, J.K. Glutathione decreases in dopaminergic PC12 cells interfere with the ubiquitin protein degradation pathway: relevance for Parkinson's disease? J. Neurochem. 80, 555–561 (2002).
  Article CAS PubMed Google Scholar
• Friguet, B. & Szweda, L.I. Inhibition of the multicatalytic proteinase (proteasome) by 4-hydroxy-2-nonenal cross-linked protein. FEBS Lett. 405, 21–25 (1997).
  Article CAS PubMed Google Scholar
• Okada, K. et al. 4-Hydroxy-2-nonenal-mediated impairment of intracellular proteolysis during oxidative stress. Identification of proteasomes as target molecules. J. Biol. Chem. 274, 23787–23793 (1999).
  Article CAS PubMed Google Scholar
• Rakhit, R. et al. Monomeric Cu,Zn-superoxide dismutase is a common misfolding intermediate in the oxidation models of sporadic and familial amyotrophic lateral sclerosis. J. Biol. Chem. 279, 15499–15504 (2004).
  Article CAS PubMed Google Scholar
• Behl, C., Davis, J.B., Lesley, R. & Schubert, D. Hydrogen peroxide mediates amyloid-β protein toxicity. Cell 77, 817–827 (1994).
  Article CAS PubMed Google Scholar
• Hsu, L.J. et al. α-Synuclein promotes mitochondrial deficit and oxidative stress. Am. J. Pathol. 157, 401–410 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Ostrerova-Golts, N. et al. The A53T α-synuclein mutation increases iron-dependent aggregation and toxicity. J. Neurosci. 20, 6048–6054 (2000).
  Article CAS PubMed Google Scholar
• Hyun, D.H. et al. Effect of wild-type or mutant Parkin on oxidative damage, nitric oxide, antioxidant defenses, and the proteasome. J. Biol. Chem. 277, 28572–28577 (2002).
  Article CAS PubMed Google Scholar
• Lee, M., Hyun, D., Jenner, P. & Halliwell, B. Effect of overexpression of wild-type and mutant Cu/Zn-superoxide dismutases on oxidative damage and antioxidant defences: relevance to Down's syndrome and familial amyotrophic lateral sclerosis. J. Neurochem. 76, 957–965 (2001).
  Article CAS PubMed Google Scholar
• Lee, M., Hyun, D.H., Halliwell, B. & Jenner, P. Effect of overexpression of wild-type and mutant Cu/Zn-superoxide dismutases on oxidative stress and cell death induced by hydrogen peroxide, 4-hydroxynonenal or serum deprivation: potentiation of injury by ALS-related mutant superoxide dismutases and protection by Bcl-2. J. Neurochem. 78, 209–220 (2001).
  Article CAS PubMed Google Scholar
• Kruman, I.I., Pedersen, W.A., Springer, J.E. & Mattson, M.P. ALS-linked Cu/Zn-SOD mutation increases vulnerability of motor neurons to excitotoxicity by a mechanism involving increased oxidative stress and perturbed calcium homeostasis. Exp. Neurol. 160, 28–39 (1999).
  Article CAS PubMed Google Scholar
• Xie, Z. et al. Peroxynitrite mediates neurotoxicity of amyloid β-peptide1–42- and lipopolysaccharide-activated microglia. J. Neurosci. 22, 3484–3492 (2002).
  Article CAS PubMed Google Scholar
• McNaught, K.S. & Jenner, P. Altered glial function causes neuronal death and increases neuronal susceptibility to 1-methyl-4-phenylpyridinium- and 6-hydroxydopamine-induced toxicity in astrocytic/ventral mesencephalic co-cultures. J. Neurochem. 73, 2469–2476 (1999).
  Article CAS PubMed Google Scholar
• Knott, C., Stern, G. & Wilkin, G.P. Inflammatory regulators in Parkinson's disease: iNOS, lipocortin-1, and cyclooxygenases-1 and -2. Mol. Cell. Neurosci. 16, 724–39 (2000).
  Article CAS PubMed Google Scholar
• Tortarolo, M. et al. Persistent activation of p38 mitogen-activated protein kinase in a mouse model of familial amyotrophic lateral sclerosis correlates with disease progression. Mol. Cell. Neurosci. 23, 180–192 (2003).
  Article CAS PubMed Google Scholar
• Drachman, D.B. et al. Cyclooxygenase 2 inhibition protects motor neurons and prolongs survival in a transgenic mouse model of ALS. Ann. Neurol. 52, 771–778 (2002).
  Article CAS PubMed Google Scholar
• Yoshihara, T. 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. 80, 158–167 (2002).
  Article CAS PubMed Google Scholar
• Marques, C.A. et al. Neurotoxic mechanisms caused by the Alzheimer's disease-linked Swedish amyloid precursor protein mutation: oxidative stress, caspases, and the JNK pathway. J. Biol. Chem. 278, 28294–28302 (2003).
  Article CAS PubMed Google Scholar
• Raoul, C. et al. Motoneuron death triggered by a specific pathway downstream of Fas. Potentiation by ALS-linked SOD1 mutations. Neuron 35, 1067–1083 (2002).
  Article CAS PubMed Google Scholar
• Saporito, M.S., Thomas, B.A. & Scott, R.W. MPTP activates c-Jun NH(2)-terminal kinase (JNK) and its upstream regulatory kinase MKK4 in nigrostriatal neurons in vivo. J. Neurochem. 75, 1200–1208 (2000).
  Article CAS PubMed Google Scholar
• Saporito, M.S., Brown, E.M., Miller, M.S. & Carswell, S. CEP-1347/KT-7515, an inhibitor of c-Jun N-terminal kinase activation, attenuates the 1-methyl-4-phenyl tetrahydropyridine-mediated loss of nigrostriatal dopaminergic neurons in vivo. J. Pharmacol. Exp. Ther. 288, 421–427 (1999).
  CAS PubMed Google Scholar
• Wang, W. et al. SP600125, a new JNK inhibitor, protects dopaminergic neurons in the MPTP model of Parkinson's disease. Neurosci. Res. 48, 195–202 (2004).
  Article CAS PubMed Google Scholar
• Xia, X.G. et al. Gene transfer of the JNK interacting protein-1 protects dopaminergic neurons in the MPTP model of Parkinson's disease. Proc. Natl. Acad. Sci. USA 98, 10433–10438 (2001).
  Article CAS PubMed Google Scholar
• Trimmer, P.A., Smith, T.S., Jung, A.B. & Bennett, J.P., Jr. Dopamine neurons from transgenic mice with a knockout of the p53 gene resist MPTP neurotoxicity. Neurodegeneration 5, 233–239 (1996).
  Article CAS PubMed Google Scholar
• Emdadul Haque, M. et al. Apoptosis-inducing neurotoxicity of dopamine and its metabolites via reactive quinone generation in neuroblastoma cells. Biochim. Biophys. Acta 1619, 39–52 (2003).
  Article CAS PubMed Google Scholar
• Canals, S., Casarejos, M.J., de Bernardo, S., Rodriguez-Martin, E. & Mena, M.A. Glutathione depletion switches nitric oxide neurotrophic effects to cell death in midbrain cultures: implications for Parkinson's disease. J. Neurochem. 79, 1183–1195 (2001).
  Article CAS PubMed Google Scholar
• Stokes, A.H. et al. Dopamine toxicity in neuroblastoma cells: role of glutathione depletion by L-BSO and apoptosis. Brain Res. 858, 1–8 (2000).
  Article CAS PubMed Google Scholar
• Betarbet, R. et al. Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat. Neurosci. 3, 1301–1306 (2000).
  Article CAS PubMed Google Scholar
• German, D.C., Liang, C.L., Manaye, K.F., Lane, K. & Sonsalla, P.K. Pharmacological inactivation of the vesicular monoamine transporter can enhance 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurodegeneration of midbrain dopaminergic neurons, but not locus coeruleus noradrenergic neurons. Neuroscience 101, 1063–1069 (2000).
  Article CAS PubMed Google Scholar
• Staal, R.G. & Sonsalla, P.K. Inhibition of brain vesicular monoamine transporter (VMAT2) enhances 1-methyl-4-phenylpyridinium neurotoxicity in vivo in rat striata. J. Pharmacol. Exp. Ther. 293, 336–342 (2000).
  CAS PubMed Google Scholar
• Gainetdinov, R.R. et al. Increased MPTP neurotoxicity in vesicular monoamine transporter 2 heterozygote knockout mice. J. Neurochem. 70, 1973–1978 (1998).
  Article CAS PubMed Google Scholar
• Takahashi, N. & Uhl, G. Murine vesicular monoamine transporter 2: molecular cloning and genomic structure. Brain Res. Mol. Brain Res. 49, 7–14 (1997).
  Article CAS PubMed Google Scholar
• Spencer, J.P. et al. Conjugates of catecholamines with cysteine and GSH in Parkinson's disease: possible mechanisms of formation involving reactive oxygen species. J. Neurochem. 71, 2112–2122 (1998).
  Article CAS PubMed Google Scholar
• Berman, S.B. & Hastings, T.G. Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: implications for Parkinson's disease. J. Neurochem. 73, 1127–1137 (1999).
  Article CAS PubMed Google Scholar
• Dexter, D.T. et al. Indices of oxidative stress and mitochondrial function in individuals with incidental Lewy body disease. Ann. Neurol. 35, 38–44 (1994).
  Article CAS PubMed Google Scholar
• Jha, N. et al. Glutathione depletion in PC12 results in selective inhibition of mitochondrial complex I activity. Implications for Parkinson's disease. J. Biol. Chem. 275, 26096–26101 (2000).
  Article CAS PubMed Google Scholar
• Barker, J.E. et al. Depletion of brain glutathione results in a decrease of glutathione reductase activity; an enzyme susceptible to oxidative damage. Brain Res. 716, 118–122 (1996).
  Article CAS PubMed Google Scholar
• Mattiazzi, M. et al. Mutated human SOD1 causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice. J. Biol. Chem. 277, 29626–29633 (2002).
  Article CAS Google Scholar
• Beretta, S. et al. Mitochondrial dysfunction due to mutant copper/zinc superoxide dismutase associated with amyotrophic lateral sclerosis is reversed by _N_-acetylcysteine. Neurobiol. Dis. 13, 213–221 (2003).
  Article CAS PubMed Google Scholar
• Khan, S.M. et al. Alzheimer's disease cybrids replicate β-amyloid abnormalities through cell death pathways. Ann. Neurol. 48, 148–155 (2000).
  Article CAS PubMed Google Scholar
• Ward, R.J. et al. Brain iron in the ferrocene-loaded rat: its chelation and influence on dopamine metabolism. Biochem. Pharmacol. 49, 1821–1826 (1995).
  Article CAS PubMed Google Scholar
• Connor, J.R. Iron acquisition and expression of iron regulatory proteins in the developing brain: manipulation by ethanol exposure, iron deprivation and cellular dysfunction. Dev. Neurosci. 16, 233–247 (1994).
  Article CAS PubMed Google Scholar
• Kaur, D. et al. Genetic or pharmacological iron chelation prevents MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's disease. Neuron 37, 899–909 (2003).
  Article CAS PubMed Google Scholar
• Cherny, R.A. et al. Treatment with a copper-zinc chelator markedly and rapidly inhibits β-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron 30, 665–676 (2001).
  Article CAS PubMed Google Scholar
• Ritchie, C.W. et al. Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Aβ amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Arch Neurol 60, 1685–1691 (2003).
  Article PubMed Google Scholar
• Hottinger, A.F., Fine, E.G., Gurney, M.E., Zurn, A.D. & Aebischer, P. The copper chelator D-penicillamine delays onset of disease and extends survival in a transgenic mouse model of familial amyotrophic lateral sclerosis. Eur. J. Neurosci. 9, 1548–1551 (1997).
  Article CAS PubMed Google Scholar
• Wiedau-Pazos, M. et al. Altered reactivity of superoxide dismutase in familial amyotrophic lateral sclerosis. Science 271, 515–518 (1996).
  Article CAS PubMed Google Scholar
• Yim, M.B. et al. A gain-of-function of an amyotrophic lateral sclerosis–associated Cu,Zn-superoxide dismutase mutant: an enhancement of free radical formation due to a decrease in _K_m for hydrogen peroxide. Proc. Natl. Acad. Sci. USA 93, 5709–5714 (1996).
  Article CAS PubMed Google Scholar
• Cudkowicz, M.E. et al. Survival in transgenic ALS mice does not vary with CNS glutathione peroxidase activity. Neurology 59, 729–734 (2002).
  Article CAS PubMed Google Scholar
• Liu, R. et al. Increased mitochondrial antioxidative activity or decreased oxygen free radical propagation prevent mutant _SOD1_-mediated motor neuron cell death and increase amyotrophic lateral sclerosis-like transgenic mouse survival. J. Neurochem. 80, 488–500 (2002).
  Article CAS PubMed Google Scholar
• Lyons, T.J. 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 93, 12240–12244 (1996).
  Article CAS PubMed Google Scholar
• Estevez, A.G. et al. Induction of nitric oxide–dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase. Science 286, 2498–2500 (1999).
  Article CAS PubMed Google Scholar
• Alexander, M.D. et al. “True” sporadic ALS associated with a novel SOD-1 mutation. Ann. Neurol. 52, 680–683 (2002).
  Article CAS PubMed Google Scholar
• Subramaniam, J.R. et al. Mutant SOD1 causes motor neuron disease independent of copper chaperone-mediated copper loading. Nat. Neurosci. 5, 301–307 (2002).
  Article CAS PubMed Google Scholar