Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 26 January 1996:
Vol. 271. no. 5248, pp. 515 - 518
DOI: 10.1126/science.271.5248.515
Prev | Table of Contents | Next

Reports

Altered Reactivity of Superoxide Dismutase in Familial Amyotrophic Lateral Sclerosis

Martina Wiedau-Pazos (1),  Joy J. Goto (1),  Shahrooz Rabizadeh,  Edith B. Gralla,  James A. Roe,  Michael K. Lee,  Joan S. Valentine (2),  Dale E. Bredesen (2)

A subset of individuals with familial amyotrophic lateral sclerosis (FALS) possesses dominantly inherited mutations in the gene that encodes copper-zinc superoxide dismutase (CuZnSOD). A4V and G93A, two of the mutant enzymes associated with FALS, were shown to catalyze the oxidation of a model substrate (spin trap 5,5'-dimethyl-1-pyrroline N-oxide) by hydrogen peroxide at a higher rate than that seen with the wild-type enzyme. Catalysis of this reaction by A4V and G93A was more sensitive to inhibition by the copper chelators diethyldithiocarbamate and penicillamine than was catalysis by wild-type CuZnSOD. The same two chelators reversed the apoptosis-inducing effect of mutant enzymes expressed in a neural cell line. These results suggest that oxidative reactions catalyzed by mutant CuZnSOD enzymes initiate the neuropathologic changes in FALS.


M. Wiedau-Pazos, J. J. Goto, E. B. Gralla, J. S. Valentine, Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA.
S. Rabizadeh, Interdepartmental Program for Neuroscience, University of California, Los Angeles, CA 90095, USA, and Program on Aging, La Jolla Cancer Research Foundation, La Jolla, CA 92037, USA.
J. A. Roe, Department of Chemistry and Biochemistry, Loyola Marymount University, Los Angeles, CA 90045, USA.
M. K. Lee, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA.
D. E. Bredesen, Program on Aging, La Jolla Cancer Research Foundation, La Jolla, CA 92037, USA.
(1) These authors contributed equally to this report.
(2) To whom correspondence should be addressed.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Changes in the Spinal Cord Proteome of an Amyotrophic Lateral Sclerosis Murine Model Determined by Differential In-gel Electrophoresis.
D. Bergemalm, K. Forsberg, P. A. Jonsson, K. S. Graffmo, T. Brannstrom, P. M. Andersen, H. Antti, and S. L. Marklund (2009)
Mol. Cell. Proteomics 8, 1306-1317
   Abstract »    Full Text »    PDF »
Transcriptional Activation in Yeast in Response to Copper Deficiency Involves Copper-Zinc Superoxide Dismutase.
L. K. Wood and D. J. Thiele (2009)
J. Biol. Chem. 284, 404-413
   Abstract »    Full Text »    PDF »
Complete Loss of Post-translational Modifications Triggers Fibrillar Aggregation of SOD1 in the Familial Form of Amyotrophic Lateral Sclerosis.
Y. Furukawa, K. Kaneko, K. Yamanaka, T. V. O'Halloran, and N. Nukina (2008)
J. Biol. Chem. 283, 24167-24176
   Abstract »    Full Text »    PDF »
The endoplasmic reticulum-Golgi pathway is a target for translocation and aggregation of mutant superoxide dismutase linked to ALS.
M. Urushitani, S. A. Ezzi, A. Matsuo, I. Tooyama, and J.-P. Julien (2008)
FASEB J 22, 2476-2487
   Abstract »    Full Text »    PDF »
A Limited Role for Disulfide Cross-linking in the Aggregation of Mutant SOD1 Linked to Familial Amyotrophic Lateral Sclerosis.
C. M. Karch and D. R. Borchelt (2008)
J. Biol. Chem. 283, 13528-13537
   Abstract »    Full Text »    PDF »
Heterodimer formation of wild-type and amyotrophic lateral sclerosis-causing mutant Cu/Zn-superoxide dismutase induces toxicity independent of protein aggregation.
H. Witan, A. Kern, I. Koziollek-Drechsler, R. Wade, C. Behl, and A. M. Clement (2008)
Hum. Mol. Genet. 17, 1373-1385
   Abstract »    Full Text »    PDF »
Oxidative Modification to Cysteine Sulfonic Acid of Cys111 in Human Copper-Zinc Superoxide Dismutase.
N. Fujiwara, M. Nakano, S. Kato, D. Yoshihara, T. Ookawara, H. Eguchi, N. Taniguchi, and K. Suzuki (2007)
J. Biol. Chem. 282, 35933-35944
   Abstract »    Full Text »    PDF »
Proteasomal Degradation of Mutant Superoxide Dismutases Linked to Amyotrophic Lateral Sclerosis.
L. Di Noto, L. J. Whitson, X. Cao, P. J. Hart, and R. L. Levine (2005)
J. Biol. Chem. 280, 39907-39913
   Abstract »    Full Text »    PDF »
Somatodendritic accumulation of misfolded SOD1-L126Z in motor neurons mediates degeneration: {alpha}B-crystallin modulates aggregation.
J. Wang, G. Xu, H. Li, V. Gonzales, D. Fromholt, C. Karch, N. G. Copeland, N. A. Jenkins, and D. R. Borchelt (2005)
Hum. Mol. Genet. 14, 2335-2347
   Abstract »    Full Text »    PDF »
Inhibition of Chaperone Activity Is a Shared Property of Several Cu,Zn-Superoxide Dismutase Mutants That Cause Amyotrophic Lateral Sclerosis.
H. Tummala, C. Jung, A. Tiwari, C. M. J. Higgins, L. J. Hayward, and Z. Xu (2005)
J. Biol. Chem. 280, 17725-17731
   Abstract »    Full Text »    PDF »
Amyotrophic Lateral Sclerosis Mutations Have the Greatest Destabilizing Effect on the Apo- and Reduced Form of SOD1, Leading to Unfolding and Oxidative Aggregation.
Y. Furukawa and T. V. O'Halloran (2005)
J. Biol. Chem. 280, 17266-17274
   Abstract »    Full Text »    PDF »
Overexpression of mutated Cu,Zn-SOD in neuroblastoma cells results in cytoskeletal change.
R. Takamiya, M. Takahashi, Y. S. Park, Y. Tawara, N. Fujiwara, Y. Miyamoto, J. Gu, K. Suzuki, and N. Taniguchi (2005)
Am J Physiol Cell Physiol 288, C253-C259
   Abstract »    Full Text »    PDF »
Dissociation of Human Copper-Zinc Superoxide Dismutase Dimers Using Chaotrope and Reductant: INSIGHTS INTO THE MOLECULAR BASIS FOR DIMER STABILITY.
P. A. Doucette, L. J. Whitson, X. Cao, V. Schirf, B. Demeler, J. S. Valentine, J. C. Hansen, and P. J. Hart (2004)
J. Biol. Chem. 279, 54558-54566
   Abstract »    Full Text »    PDF »
Mitochondrial Protein Oxidation in Yeast Mutants Lacking Manganese-(MnSOD) or Copper- and Zinc-containing Superoxide Dismutase (CuZnSOD): EVIDENCE THAT MnSOD AND CuZnSOD HAVE BOTH UNIQUE AND OVERLAPPING FUNCTIONS IN PROTECTING MITOCHONDRIAL PROTEINS FROM OXIDATIVE DAMAGE.
K. M. O'Brien, R. Dirmeier, M. Engle, and R. O. Poyton (2004)
J. Biol. Chem. 279, 51817-51827
   Abstract »    Full Text »    PDF »
Increased internalisation and degradation of GLT-1 glial glutamate transporter in a cell model for familial amyotrophic lateral sclerosis (ALS).
C. Vanoni, S. Massari, M. Losa, P. Carrega, C. Perego, L. Conforti, and G. Pietrini (2004)
J. Cell Sci. 117, 5417-5426
   Abstract »    Full Text »    PDF »
Genetically Decreased Spinal Cord Copper Concentration Prolongs Life in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis.
M. Kiaei, A. I. Bush, B. M. Morrison, J. H. Morrison, R. A. Cherny, I. Volitakis, M. F. Beal, and J. W. Gordon (2004)
J. Neurosci. 24, 7945-7950
   Abstract »    Full Text »    PDF »
Alsin, the Product of ALS2 Gene, Suppresses SOD1 Mutant Neurotoxicity through RhoGEF Domain by Interacting with SOD1 Mutants.
K. Kanekura, Y. Hashimoto, T. Niikura, S. Aiso, M. Matsuoka, and I. Nishimoto (2004)
J. Biol. Chem. 279, 19247-19256
   Abstract »    Full Text »    PDF »
From the Cover: Dimer destabilization in superoxide dismutase may result in disease-causing properties: Structures of motor neuron disease mutants.
M. A. Hough, J. G. Grossmann, S. V. Antonyuk, R. W. Strange, P. A. Doucette, J. A. Rodriguez, L. J. Whitson, P. J. Hart, L. J. Hayward, J. S. Valentine, et al. (2004)
PNAS 101, 5976-5981
   Abstract »    Full Text »    PDF »
Molecular signature of late-stage human ALS revealed by expression profiling of postmortem spinal cord gray matter.
F. Dangond, D. Hwang, S. Camelo, P. Pasinelli, M. P. Frosch, G. Stephanopoulos, G. Stephanopoulos, R. H. Brown Jr., and S. R. Gullans (2004)
Physiol Genomics 16, 229-239
   Abstract »    Full Text »    PDF »
Copper-binding-site-null SOD1 causes ALS in transgenic mice: aggregates of non-native SOD1 delineate a common feature.
J. Wang, H. Slunt, V. Gonzales, D. Fromholt, M. Coonfield, N. G. Copeland, N. A. Jenkins, and D. R. Borchelt (2003)
Hum. Mol. Genet. 12, 2753-2764
   Abstract »    Full Text »    PDF »
Wild-Type Nonneuronal Cells Extend Survival of SOD1 Mutant Motor Neurons in ALS Mice.
A. M. Clement, M. D. Nguyen, E. A. Roberts, M. L. Garcia, S. Boillee, M. Rule, A. P. McMahon, W. Doucette, D. Siwek, R. J. Ferrante, et al. (2003)
Science 302, 113-117
   Abstract »    Full Text »    PDF »
Retrograde Viral Delivery of IGF-1 Prolongs Survival in a Mouse ALS Model.
B. K. Kaspar, J. Llado, N. Sherkat, J. D. Rothstein, and F. H. Gage (2003)
Science 301, 839-842
   Abstract »    Full Text »    PDF »
Bicarbonate-dependent Peroxidase Activity of Human Cu,Zn-Superoxide Dismutase Induces Covalent Aggregation of Protein: INTERMEDIACY OF TRYPTOPHAN-DERIVED OXIDATION PRODUCTS.
H. Zhang, C. Andrekopoulos, J. Joseph, K. Chandran, H. Karoui, J. P. Crow, and B. Kalyanaraman (2003)
J. Biol. Chem. 278, 24078-24089
   Abstract »    Full Text »    PDF »
An Alternative Mechanism of Bicarbonate-mediated Peroxidation by Copper-Zinc Superoxide Dismutase: RATES ENHANCED VIA PROPOSED ENZYME-ASSOCIATED PEROXYCARBONATE INTERMEDIATE.
J. S. Elam, K. Malek, J. A. Rodriguez, P. A. Doucette, A. B. Taylor, L. J. Hayward, D. E. Cabelli, J. S. Valentine, and P. J. Hart (2003)
J. Biol. Chem. 278, 21032-21039
   Abstract »    Full Text »    PDF »
Bioinorganic Chemistry Special Feature: Misfolded CuZnSOD and amyotrophic lateral sclerosis.
J. S. Valentine and P. J. Hart (2003)
PNAS 100, 3617-3622
   Abstract »    Full Text »    PDF »
Common denominator of Cu/Zn superoxide dismutase mutants associated with amyotrophic lateral sclerosis: Decreased stability of the apo state.
M. J. Lindberg, L. Tibell, and M. Oliveberg (2002)
PNAS 99, 16607-16612
   Abstract »    Full Text »    PDF »
Oxidation-induced Misfolding and Aggregation of Superoxide Dismutase and Its Implications for Amyotrophic Lateral Sclerosis.
R. Rakhit, P. Cunningham, A. Furtos-Matei, S. Dahan, X.-F. Qi, J. P. Crow, N. R. Cashman, L. H. Kondejewski, and A. Chakrabartty (2002)
J. Biol. Chem. 277, 47551-47556
   Abstract »    Full Text »    PDF »
Survival in transgenic ALS mice does not vary with CNS glutathione peroxidase activity.
M. E. Cudkowicz, K. A. Pastusza, P. C. Sapp, R. K. Mathews, J. Leahy, P. Pasinelli, J. W. Francis, D. Jiang, J. K. Andersen, and R. H. Brown Jr. (2002)
Neurology 59, 729-734
   Abstract »    Full Text »    PDF »
Mutated Human SOD1 Causes Dysfunction of Oxidative Phosphorylation in Mitochondria of Transgenic Mice.
M. Mattiazzi, M. D'Aurelio, C. D. Gajewski, K. Martushova, M. Kiaei, M. F. Beal, and G. Manfredi (2002)
J. Biol. Chem. 277, 29626-29633
   Abstract »    Full Text »    PDF »
Mitochondrial dysfunction in a cell culture model of familial amyotrophic lateral sclerosis.
F. M. Menzies, M. R. Cookson, R. W. Taylor, D. M. Turnbull, Z. M. A. Chrzanowska-Lightowlers, L. Dong, D. A. Figlewicz, and P. J. Shaw (2002)
Brain 125, 1522-1533
   Abstract »    Full Text »    PDF »
Decreased Metallation and Activity in Subsets of Mutant Superoxide Dismutases Associated with Familial Amyotrophic Lateral Sclerosis.
L. J. Hayward, J. A. Rodriguez, J. W. Kim, A. Tiwari, J. J. Goto, D. E. Cabelli, J. S. Valentine, and R. H. Brown Jr. (2002)
J. Biol. Chem. 277, 15923-15931
   Abstract »    Full Text »    PDF »
Histidinyl Radical Formation in the Self-peroxidation Reaction of Bovine Copper-Zinc Superoxide Dismutase.
M. R. Gunther, J. A. Peters, and M. K. Sivaneri (2002)
J. Biol. Chem. 277, 9160-9166
   Abstract »    Full Text »    PDF »
The "new" mitochondrial disorders.
A H V Schapira (2002)
J. Neurol. Neurosurg. Psychiatry 72, 144-149
   Abstract »    Full Text »    PDF »
Extracellular Superoxide Dismutase, Uric Acid, and Atherosclerosis.
H.U. HINK and T. FUKAI (2002)
Cold Spring Harb Symp Quant Biol 67, 483-490
   Abstract »    PDF »
Mechanisms of neurodegeneration in amyotrophic lateral sclerosis.
S Cluskey and D B Ramsden (2001)
Mol. Pathol. 54, 386-392
   Abstract »    Full Text »    PDF »
Accelerated S-Nitrosothiol Breakdown by Amyotrophic Lateral Sclerosis Mutant Copper,Zinc-Superoxide Dismutase.
M. A. Johnson, T. L. Macdonald, J. B. Mannick, M. R. Conaway, and B. Gaston (2001)
J. Biol. Chem. 276, 39872-39878
   Abstract »    Full Text »    PDF »
Oxidative stress causes abnormal accumulation of familial amyotrophic lateral sclerosis-related mutant SOD1 in transgenic Caenorhabditis elegans.
T. Oeda, S. Shimohama, N. Kitagawa, R. Kohno, T. Imura, H. Shibasaki, and N. Ishii (2001)
Hum. Mol. Genet. 10, 2013-2023
   Abstract »    Full Text »    PDF »
From the Cover: Essential role for mammalian copper transporter Ctr1 in copper homeostasis and embryonic development.
J. Lee, J. R. Prohaska, and D. J. Thiele (2001)
PNAS 98, 6842-6847
   Abstract »    Full Text »    PDF »
Delaying Caspase Activation by Bcl-2: A Clue to Disease Retardation in a Transgenic Mouse Model of Amyotrophic Lateral Sclerosis.
S. Vukosavic, L. Stefanis, V. Jackson-Lewis, C. Guegan, N. Romero, C. Chen, M. Dubois-Dauphin, and S. Przedborski (2000)
J. Neurosci. 20, 9119-9125
   Abstract »    Full Text »    PDF »
RGC Death in Mice after Optic Nerve Crush Injury: Oxidative Stress and Neuroprotection.
H. Levkovitch–Verbin, C. Harris–Cerruti, Y. Groner, L. A. Wheeler, M. Schwartz, and E. Yoles (2000)
Invest. Ophthalmol. Vis. Sci. 41, 4169-4174
   Abstract »    Full Text »
Bicarbonate Enhances the Hydroxylation, Nitration, and Peroxidation Reactions Catalyzed by Copper, Zinc Superoxide Dismutase. INTERMEDIACY OF CARBONATE ANION RADICAL.
H. Zhang, J. Joseph, C. Felix, and B. Kalyanaraman (2000)
J. Biol. Chem. 275, 14038-14045
   Abstract »    Full Text »    PDF »
The prostate apoptosis response-4 protein participates in motor neuron degeneration in amyotrophic lateral sclerosis.
W. A. PEDERSEN, H. LUO, I. KRUMAN, E. KASARSKIS, and M. P. MATTSON (2000)
FASEB J 14, 913-924
   Abstract »    Full Text »
Nerve Growth Factor-induced Neuronal Differentiation Requires Generation of Rac1-regulated Reactive Oxygen Species.
K. Suzukawa, K. Miura, J. Mitsushita, J. Resau, K. Hirose, R. Crystal, and T. Kamata (2000)
J. Biol. Chem. 275, 13175-13178
   Abstract »    Full Text »    PDF »
Toxicity of ALS-Linked SOD1 Mutants.
T. L. Williamson, L. B. Corson, L. Huang, A. Burlingame, J. Liu, L. I. Bruijn, D. W. Cleveland;, J. S. Beckman, J. P. Crow, and A. G. Estévez; (2000)
Science 288, 399a-399
   Full Text »
Cu,Zn-Superoxide Dismutase-dependent Apoptosis Induced by Nitric Oxide in Neuronal Cells.
M. R. Ciriolo, A. De Martino, E. Lafavia, L. Rossi, M. T. Carri, and G. Rotilio (2000)
J. Biol. Chem. 275, 5065-5072
   Abstract »    Full Text »    PDF »
Loss of in Vitro Metal Ion Binding Specificity in Mutant Copper-Zinc Superoxide Dismutases Associated with Familial Amyotrophic Lateral Sclerosis.
J. J. Goto, H. Zhu, R. J. Sanchez, A. Nersissian, E. B. Gralla, J. S. Valentine, and D. E. Cabelli (2000)
J. Biol. Chem. 275, 1007-1014
   Abstract »    Full Text »    PDF »
A Gain of Superoxide Dismutase (SOD) Activity Obtained with CCS, the Copper Metallochaperone for SOD1.
P. J. Schmidt, M. Ramos-Gomez, and V. C. Culotta (1999)
J. Biol. Chem. 274, 36952-36956
   Abstract »    Full Text »    PDF »
Evidence against the Generation of Free Hydroxyl Radicals from the Interaction of Copper,Zinc-Superoxide Dismutase and Hydrogen Peroxide.
S. Sankarapandi and J. L. Zweier (1999)
J. Biol. Chem. 274, 34576-34583
   Abstract »    Full Text »    PDF »
Negative Regulation of the Gene for Fe-Containing Superoxide Dismutase by an Ni-Responsive Factor in Streptomyces coelicolor.
H.-J. Chung, J.-H. Choi, E.-J. Kim, Y.-H. Cho, and J.-H. Roe (1999)
J. Bacteriol. 181, 7381-7384
   Abstract »    Full Text »
The roles of free radicals in amyotrophic lateral sclerosis: reactive oxygen species and elevated oxidation of protein, DNA, and membrane phospholipids.
D. LIU, J. WEN, J. LIU, and L. LI (1999)
FASEB J 13, 2318-2328
   Abstract »    Full Text »
The Alzheimer's Disease Amyloid Precursor Protein Modulates Copper-Induced Toxicity and Oxidative Stress in Primary Neuronal Cultures.
A. R. White, G. Multhaup, F. Maher, S. Bellingham, J. Camakaris, H. Zheng, A. I. Bush, K. Beyreuther, C. L. Masters, and R. Cappai (1999)
J. Neurosci. 19, 9170-9179
   Abstract »    Full Text »    PDF »
Bicarbonate Enhances the Peroxidase Activity of Cu,Zn-Superoxide Dismutase. ROLE OF CARBONATE ANION RADICAL.
S. P. A. Goss, R. J. Singh, and B. Kalyanaraman (1999)
J. Biol. Chem. 274, 28233-28239
   Abstract »    Full Text »    PDF »
The role of immunophilins in mutant superoxide dismutase-1linked familial amyotrophic lateral sclerosis.
J.-p. Lee, H. C. Palfrey, V. P. Bindokas, G. D. Ghadge, L. Ma, R. J. Miller, and R. P. Roos (1999)
PNAS 96, 3251-3256
   Abstract »    Full Text »    PDF »
Bicarbonate Is Required for the Peroxidase Function of Cu,Zn-Superoxide Dismutase at Physiological pH.
S. Sankarapandi and J. L. Zweier (1999)
J. Biol. Chem. 274, 1226-1232
   Abstract »    Full Text »    PDF »
Caspase-1 is activated in neural cells and tissue with amyotrophic lateral sclerosis-associated mutations in copper-zinc superoxide dismutase.
P. Pasinelli, D. R. Borchelt, M. K. Houseweart, D. W. Cleveland, and R. H. Brown Jr. (1998)
PNAS 95, 15763-15768
   Abstract »    Full Text »    PDF »
Glutamate Potentiates the Toxicity of Mutant Cu/Zn-Superoxide Dismutase in Motor Neurons by Postsynaptic Calcium-Dependent Mechanisms.
J. Roy, S. Minotti, L. Dong, D. A. Figlewicz, and H. D. Durham (1998)
J. Neurosci. 18, 9673-9684
   Abstract »    Full Text »    PDF »
Reactions of Hydrogen Peroxide with Familial Amyotrophic Lateral Sclerosis Mutant Human Copper-Zinc Superoxide Dismutases Studied by Pulse Radiolysis.
J. J. Goto, E. B. Gralla, J. S. Valentine, and D. E. Cabelli (1998)
J. Biol. Chem. 273, 30104-30109
   Abstract »    Full Text »    PDF »
Genetic Neurodegenerative Diseases: The Human Illness and Transgenic Models.
D. L. Price, S. S. Sisodia, and D. R. Borchelt (1998)
Science 282, 1079-1083
   Abstract »    Full Text »
Nitration of gamma -tocopherol and oxidation of alpha -tocopherol by copper-zinc superoxide dismutase/H2O2/NO2-: Role of nitrogen dioxide free radical.
R. J. Singh, S. P. A. Goss, J. Joseph, and B. Kalyanaraman (1998)
PNAS 95, 12912-12917
   Abstract »    Full Text »    PDF »
Aggregation and Motor Neuron Toxicity of an ALS-Linked SOD1 Mutant Independent from Wild-Type SOD1.
L. I. Bruijn, M. K. Houseweart, S. Kato, K. L. Anderson, S. D. Anderson, E. Ohama, A. G. Reaume, R. W. Scott, and D. W. Cleveland (1998)
Science 281, 1851-1854
   Abstract »    Full Text »
The Copper Chaperone CCS Directly Interacts with Copper/Zinc Superoxide Dismutase.
R. L. B. Casareno, D. Waggoner, and J. D. Gitlin (1998)
J. Biol. Chem. 273, 23625-23628
   Abstract »    Full Text »    PDF »
A Glutamate Bridge Is Essential for Dimer Stability and Metal Selectivity in Manganese Superoxide Dismutase.
M. M. Whittaker and J. W. Whittaker (1998)
J. Biol. Chem. 273, 22188-22193
   Abstract »    Full Text »    PDF »
Protective effect of neurofilament heavy gene overexpression in motor neuron disease induced by mutant superoxide dismutase.
S. Couillard-Despres, Q. Zhu, P. C. Wong, D. L. Price, D. W. Cleveland, and J.-P. Julien (1998)
PNAS 95, 9626-9630
   Abstract »    Full Text »    PDF »
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.
T. L. Williamson, L. I. Bruijn, Q. Zhu, K. L. Anderson, S. D. Anderson, J.-P. Julien, and D. W. Cleveland (1998)
PNAS 95, 9631-9636
   Abstract »    Full Text »    PDF »
Experimental Destruction of Substantia Nigra Initiated by Parkinson Disease Immunoglobulins.
S. Chen, W. D. Le, W. J. Xie, M. E. Alexianu, J. I. Engelhardt, L. Siklos, and S. H. Appel (1998)
Arch Neurol 55, 1075-1080
   Abstract »    Full Text »    PDF »
Reexamination of the mechanism of hydroxyl radical adducts formed from the reaction between familial amyotrophic lateral sclerosis-associated Cu,Zn superoxide dismutase mutants and H2O2.
R. J. Singh, H. Karoui, M. R. Gunther, J. S. Beckman, R. P. Mason, and B. Kalyanaraman (1998)
PNAS 95, 6675-6680
   Abstract »    Full Text »    PDF »
Alzheimer's disease, amyotrophic lateral sclerosis, and transgenic mice.
N P S BAJAJ, N G IRVING, P N LEIGH, and C C J MILLER (1998)
J. Neurol. Neurosurg. Psychiatry 64, 711-715
   Full Text »    PDF »
Chaperone-facilitated copper binding is a property common to several classes of familial amyotrophic lateral sclerosis-linked superoxide dismutase mutants.
L. B. Corson, J. J. Strain, V. C. Culotta, and D. W. Cleveland (1998)
PNAS 95, 6361-6366
   Abstract »    Full Text »    PDF »
Massive Mitochondrial Degeneration in Motor Neurons Triggers the Onset of Amyotrophic Lateral Sclerosis in Mice Expressing a Mutant SOD1.
J. Kong and Z. Xu (1998)
J. Neurosci. 18, 3241-3250
   Abstract »    Full Text »    PDF »
Overexpression of human copper,zinc-superoxide dismutase (SOD1) prevents postischemic injury.
P. Wang, H. Chen, H. Qin, S. Sankarapandi, M. W. Becher, P. C. Wong, and J. L. Zweier (1998)
PNAS 95, 4556-4560
   Abstract »    Full Text »    PDF »
HAH1 Is a Copper-binding Protein with Distinct Amino Acid Residues Mediating Copper Homeostasis and Antioxidant Defense.
I. H. Hung, R. L. B. Casareno, G. Labesse, F. S. Mathews, and J. D. Gitlin (1998)
J. Biol. Chem. 273, 1749-1754
   Abstract »    Full Text »    PDF »
Selegiline Is Ineffective in a Collaborative Double-blind, Placebo-Controlled Trial for Treatment of Amyotrophic Lateral Sclerosis.
D. J. Lange, P. L. Murphy, B. Diamond, V. Appel, E. C. Lai, D. S. Younger, and S. H. Appel (1998)
Arch Neurol 55, 93-96
   Abstract »    Full Text »    PDF »
Peroxynitrite rapidly permeates phospholipid membranes.
S. S. Marla, J. Lee, and J. T. Groves (1997)
PNAS 94, 14243-14248
   Abstract »    Full Text »    PDF »
Mutant Superoxide Dismutase-1-Linked Familial Amyotrophic Lateral Sclerosis: Molecular Mechanisms of Neuronal Death and Protection.
G. D. Ghadge, J. P. Lee, V. P. Bindokas, J. Jordan, L. Ma, R. J. Miller, and R. P. Roos (1997)
J. Neurosci. 17, 8756-8766
   Abstract »    Full Text »    PDF »
Identification of the prooxidant site of human ceruloplasmin: A model for oxidative damage by copper bound to protein surfaces.
C. K. Mukhopadhyay, B. Mazumder, P. F. Lindley, and P. L. Fox (1997)
PNAS 94, 11546-11551
   Abstract »    Full Text »    PDF »
Developmental disorder associated with increased cellular nucleotidase activity.
T. Page, A. Yu, J. Fontanesi, and W. L. Nyhan (1997)
PNAS 94, 11601-11606
   Abstract »    Full Text »    PDF »
Amyotrophic Lateral Sclerosis: Insights From Genetics.
R. H. Brown Jr (1997)
Arch Neurol 54, 1246-1250
   Abstract »    PDF »
The Copper Chaperone for Superoxide Dismutase.
V. C. Culotta, L. W. J. Klomp, J. Strain, R. L. B. Casareno, B. Krems, and J. D. Gitlin (1997)
J. Biol. Chem. 272, 23469-23472
   Abstract »    Full Text »    PDF »
Carboxyfullerenes as neuroprotective agents.
L. L. Dugan, D. M. Turetsky, C. Du, D. Lobner, M. Wheeler, C. R. Almli, C. K.-F. Shen, T.-Y. Luh, D. W. Choi, and T.-S. Lin (1997)
PNAS 94, 9434-9439
   Abstract »    Full Text »    PDF »
Superoxide Anion Radical (Obardot 2), Superoxide Dismutases, and Related Matters.
I. Fridovich (1997)
J. Biol. Chem. 272, 18515-18517
   Full Text »    PDF »
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.
L. I. Bruijn, M. F. Beal, M. W. Becher, J. B. Schulz, P. C. Wong, D. L. Price, and D. W. Cleveland (1997)
PNAS 94, 7606-7611
   Abstract »    Full Text »    PDF »
Neurology.
R. J. Joynt and R. M. Kurlan (1997)
JAMA 277, 1873-1874
   PDF »
Oxidative stress mediates impairment of muscle function in transgenic mice with elevated level of wild-type Cu/Zn superoxide dismutase.
M. Peled-Kamar, J. Lotem, I. Wirguin, L. Weiner, A. Hermalin, and Y. Groner (1997)
PNAS 94, 3883-3887
   Abstract »    Full Text »    PDF »
A Familial Amyotrophic Lateral Sclerosis-associated A4V Cu,Zn-Superoxide Dismutase Mutant Has a Lower Km for Hydrogen Peroxide. CORRELATION BETWEEN CLINICAL SEVERITY AND THE Km VALUE.
H.-S. Yim, J.-H. Kang, P. B. Chock, E. R. Stadtman, and M. B. Yim (1997)
J. Biol. Chem. 272, 8861-8863
   Abstract »    Full Text »    PDF »
Identification and Functional Expression of HAH1, a Novel Human Gene Involved in Copper Homeostasis.
L. W.J. Klomp, S.-J. Lin, D. S.Y. R. D. Klausner, V. C. Culotta, and J. D. Gitlin (1997)
J. Biol. Chem. 272, 9221-9226
   Abstract »    Full Text »    PDF »
Suppression of Nerve Growth Factor-induced Neuronal Differentiation of PC12 Cells. N-ACETYLCYSTEINE UNCOUPLES THE SIGNAL TRANSDUCTION FROM Ras TO THE MITOGEN-ACTIVATED PROTEIN KINASE CASCADE.
H. Kamata, C. Tanaka, H. Yagisawa, S. Matsuda, Y. Gotoh, E. Nishida, and H. Hirata (1996)
J. Biol. Chem. 271, 33018-33025
   Abstract »    Full Text »    PDF »
Assessment of normal and mutant human presenilin function in Caenorhabditis elegans.
D. Levitan, T. G. Doyle, D. Brousseau, M. K. Lee, G. Thinakaran, H. H. Slunt, S. S. Sisodia, and I. Greenwald (1996)
PNAS 93, 14940-14944
   Abstract »    Full Text »    PDF »
Initiation of Runaway Cell Death in an Arabidopsis Mutant by Extracellular Superoxide.
T. Jabs, R. A. Dietrich, and J. L. Dangl (1996)
Science 273, 1853-1856
   Abstract »    Full Text »
REVIEW {blacksquare} : Keeping Neurons Alive: The Molecular Control of Apoptosis (Part I.
D. E. Bredesen (1996)
Neuroscientist 2, 181-190
   Abstract »    PDF »
ALS: Molecular Clues to the Jigsaw Puzzle of Neuronal Degeneration.
T. Siddique (1996)
Cold Spring Harb Symp Quant Biol 61, 699-708
   Abstract »    PDF »
Neurofilaments, Radial Growth of Axons, and Mechanisms of Motor Neuron Disease.
T.L. Williamson, J.R. Marszalek, J.D. Vechio, L.I. Bruijn, M.K. Lee, Z. Xu, R.H. Brown Jr., and D.W. Cleveland (1996)
Cold Spring Harb Symp Quant Biol 61, 709-723
   Abstract »    PDF »
Neurodegenerative Diseases and Model Systems.
D.L. Price, D.R. Borchelt, P.C. Wong, C.A. Pardo, G. Thinakaran, M.K. Lee, D.W. Cleveland, and S.S. Sisodia (1996)
Cold Spring Harb Symp Quant Biol 61, 725-738
   Abstract »    PDF »
Bicarbonate Enhances Peroxidase Activity of Cu,Zn-Superoxide Dismutase. ROLE OF CARBONATE ANION RADICAL AND SCAVENGING OF CARBONATE ANION RADICAL BY METALLOPORPHYRIN ANTIOXIDANT ENZYME MIMETICS.
H. Zhang, J. Joseph, M. Gurney, D. Becker, and B. Kalyanaraman (2002)
J. Biol. Chem. 277, 1013-1020
   Abstract »    Full Text »    PDF »
Copper chaperone for superoxide dismutase is essential to activate mammalian Cu/Zn superoxide dismutase.
P. C. Wong, D. Waggoner, J. R. Subramaniam, L. Tessarollo, T. B. Bartnikas, V. C. Culotta, D. L. Price, J. Rothstein, and J. D. Gitlin (2000)
PNAS 97, 2886-2891
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)