DOI: 10.1126/science.281.5384.1851. Aggregation and Motor Neuron Toxicity of an ALS-Linked SOD1 Mutant Independent from Wild-Type SOD1

Aggregation and Motor Neuron Toxicity of an ALS-Linked SOD1 Mutant Independent from Wild-Type SOD1

10.1126/science.281.5384.1851

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Analysis of transgenic mice expressing familial amyotrophic lateral sclerosis (ALS)–linked mutations in the enzyme superoxide dismutase (SOD1) have shown that motor neuron death arises from a mutant-mediated toxic property or properties. In testing the disease mechanism, both elimination and elevation of wild-type SOD1 were found to have no effect on mutant-mediated disease, which demonstrates that the use of SOD mimetics is unlikely to be an effective therapy and raises the question of whether toxicity arises from superoxide-mediated oxidative stress. Aggregates containing SOD1 were common to disease caused by different mutants, implying that coaggregation of an unidentified essential component or components or aberrant catalysis by misfolded mutants underlies a portion of mutant-mediated toxicity.

Bibliography

Bruijn, L. I., Houseweart, M. K., Kato, S., Anderson, K. L., Anderson, S. D., Ohama, E., Reaume, A. G., Scott, R. W., & Cleveland, D. W. (1998). Aggregation and Motor Neuron Toxicity of an ALS-Linked SOD1 Mutant Independent from Wild-Type SOD1. Science, 281(5384), 1851â1854.

Authors 9

Lucie I. Bruijn (first)
Megan K. Houseweart (additional)
Shinsuke Kato (additional)
Karen L. Anderson (additional)
Scott D. Anderson (additional)
Eisaku Ohama (additional)
Andrew G. Reaume (additional)
Rick W. Scott (additional)
Don W. Cleveland (additional)

References 38 Referenced 976

Rosen D. R., et al., Nature 362, 59 (1993). (10.1038/362059a0) / Nature by Rosen D. R. (1993)
Gurney M. E., et al., Science 264, 1772 (1994). (10.1126/science.8209258) / Science by Gurney M. E. (1994)
Ripps M. E., Huntley G. W., Hof P. R., Morrison J. H., Gordon J. W., Proc. Natl. Acad. Sci. U.S.A. 92, 689 (1995). (10.1073/pnas.92.3.689) / Proc. Natl. Acad. Sci. U.S.A. by Ripps M. E. (1995)
Wong P. C., et al., Neuron 14, 1105 (1995). (10.1016/0896-6273(95)90259-7) / Neuron by Wong P. C. (1995)
Bruijn L. I., et al., ibid. 18, 327 (1997). / ibid. by Bruijn L. I. (1997)
Beckman J. S., Carson M., Smith C. D., Koppenol W. H., Nature 364, 584 (1993). (10.1038/364584a0) / Nature by Beckman J. S. (1993)
10.1126/science.271.5248.515
Liochev S. I., Chen L. L., Hallewell R. A., Fridovich I., Arch. Biochem. Biophys. 346, 263 (1997). (10.1006/abbi.1997.0298) / Arch. Biochem. Biophys. by Liochev S. I. (1997)
10.1126/science.8351519
Orrell R., Belleroche J., Marklund S., Bowe F., Hallewell R., Nature 274, 504 (1995). (10.1038/374504a0) / Nature by Orrell R. (1995)
Durham H. D., Roy J., Dong L., Figlewicz D. A., J. Neuropathol. Exp. Neurol. 56, 52 (1997). (10.1097/00005072-199705000-00008) / J. Neuropathol. Exp. Neurol. by Durham H. D. (1997)
Corson L. B., Strain J., Culotta V. C., Cleveland D. W., Proc. Natl. Acad. Sci. U.S.A. 95, 6361 (1998). (10.1073/pnas.95.11.6361) / Proc. Natl. Acad. Sci. U.S.A. by Corson L. B. (1998)
SOD1 G85R mice (line 148) (5) were bred to mice overexpressing human wild-type SOD1 (hSOD1 line 30) (4) to six times the level of endogenous SOD1. SOD1 G85R mice were bred with mice heterozygous for SOD1 deletion (SOD1 +/– ) to generate SOD1 G85R SOD1 +/– mice which were then bred with SOD1 +/− mice to generate in the same litters SOD1 G85R mice with zero one or two copies of the endogenous SOD1 gene as well as normal nontransgenic mice.
Reaume A. G., et al., Nature Genet. 13, 43 (1996). (10.1038/ng0596-43) / Nature Genet. by Reaume A. G. (1996)
Immunoblots (70 μg of total spinal cord homogenates) were incubated with polyclonal antipeptide antibodies generated against a sequence present in human but not mouse SOD1 or against antipeptide antibodies specific for mouse SOD1 (5). Signals were detected with 125 I-labeled protein A and quantified by phosphorImaging.
Dal Canto M. C., Gurney M. E., Acta Neuropathol. 93, 537 (1997). (10.1007/s004010050650) / Acta Neuropathol. by Dal Canto M. C. (1997)
M. Becher and D. L. Price personal communication.
Shibata N., et al., Neurosci. Lett. 179, 149 (1994). (10.1016/0304-3940(94)90956-3) / Neurosci. Lett. by Shibata N. (1994)
Chou S. M., Wang H. S., Komai K., J. Chem. Neuroanat. 10, 249 (1996). (10.1016/0891-0618(96)00137-8) / J. Chem. Neuroanat. by Chou S. M. (1996)
Shibata N., Asayama K., Hirano A., Kobayashi M., Dev. Neurosci. 18, 492 (1996). (10.1159/000111445) / Dev. Neurosci. by Shibata N. (1996)
Chou S. M., Wang H. S., Taniguchi A., J. Neurol. Sci. 139, 16 (1996). (10.1016/0022-510X(96)00090-1) / J. Neurol. Sci. by Chou S. M. (1996)
Shibata N., et al., J. Neuropathol. Exp. Neurol. 55, 481 (1996). (10.1097/00005072-199604000-00011) / J. Neuropathol. Exp. Neurol. by Shibata N. (1996)
S. Kato et al. ibid. p. 1089.
Kato S., et al., Am. J. Pathol. 151, 611 (1997). / Am. J. Pathol. by Kato S. (1997)
Pardo C. A., et al., Proc. Natl. Acad. Sci. U.S.A. 92, 954 (1995). (10.1073/pnas.92.4.954) / Proc. Natl. Acad. Sci. U.S.A. by Pardo C. A. (1995)
Liochev S. I., Chen L. L., Hallewell R. A., Fridovich I., Arch. Biochem. Biophys. 346, 263 (1997). (10.1006/abbi.1997.0298) / Arch. Biochem. Biophys. by Liochev S. I. (1997)
Yim H. S., Kang J. H., Chock P. B., Stadtman E. R., Yim M. B., J. Biol. Chem. 272, 8861 (1997). (10.1074/jbc.272.14.8861) / J. Biol. Chem. by Yim H. S. (1997)
Bruijn L., et al., Proc. Natl Acad. Sci. U.S.A. 94, 7606 (1997). (10.1073/pnas.94.14.7606) / Proc. Natl Acad. Sci. U.S.A. by Bruijn L. (1997)
Ferrante R. J., et al., Ann. Neurol. 42, 326 (1997). (10.1002/ana.410420309) / Ann. Neurol. by Ferrante R. J. (1997)
M. F. Beal et al. ibid. p. 646.
Singh R. J., et al., Proc. Natl. Acad. Sci. U.S.A. 95, 6675 (1998). (10.1073/pnas.95.12.6675) / Proc. Natl. Acad. Sci. U.S.A. by Singh R. J. (1998)
Bowling A. C., Schulz J. B., Brown R. H., Beal M. F., J. Neurochem. 61, 2322 (1993); (10.1111/j.1471-4159.1993.tb07478.x) / J. Neurochem. by Bowling A. C. (1993)
10.1126/science.266.5190.1586.b
McNamara J. O., Fridovich I., Nature 362, 20 (1993). (10.1038/362020a0) / Nature by McNamara J. O. (1993)
T. L. Williamson and D. W. Cleveland unpublished data.
Williamson T. L., et al., Proc. Natl. Acad. Sci. U.S.A. 95, 9631 (1998). (10.1073/pnas.95.16.9631) / Proc. Natl. Acad. Sci. U.S.A. by Williamson T. L. (1998)
Histology and immunocytochemistry were performed as described (5) using antibodies to glial fibrillary acidic protein (DAKO Carpinteria CA) or SOD1 (5 25). For restaining of sections after treatment with hemotoxylin and eosin (H&E) coverslips were removed and decolorized with 1% HCl in 70% ethanol before immunocytochemistry.
We are grateful to L. B. Corson for critical reading of the manuscript and to H. Hwang for her technical assistance. This work was supported by grants to D.W.C. from NIH (NS 27036) and the ALS Association. L.I.B. was supported by a postdoctoral fellowship from the Muscular Dystrophy Association. Salary support for D.W.C. is provided by the Ludwig Institute for Cancer Research. S.K. is supported by a Grant-in-Aid for Scientific Research (09680744) from the Ministry of Education Science Sports and Culture of Japan.

Dates

Type	When
Created	23 years, 1 month ago (July 27, 2002, 5:43 a.m.)
Deposited	1 year, 7 months ago (Jan. 12, 2024, 10:28 p.m.)
Indexed	10 hours, 33 minutes ago (Aug. 31, 2025, 7:11 p.m.)
Issued	26 years, 11 months ago (Sept. 18, 1998)
Published	26 years, 11 months ago (Sept. 18, 1998)
Published Print	26 years, 11 months ago (Sept. 18, 1998)

Funders 0

None

BibTeX

@article{Bruijn_1998, title={Aggregation and Motor Neuron Toxicity of an ALS-Linked SOD1 Mutant Independent from Wild-Type SOD1}, volume={281}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.281.5384.1851}, DOI={10.1126/science.281.5384.1851}, number={5384}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Bruijn, Lucie I. and Houseweart, Megan K. and Kato, Shinsuke and Anderson, Karen L. and Anderson, Scott D. and Ohama, Eisaku and Reaume, Andrew G. and Scott, Rick W. and Cleveland, Don W.}, year={1998}, month=sep, pages={1851–1854} }

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      "year": "1996",
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      "author": "Shibata N.",
      "year": "1996",
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      "journal-title": "J. Neuropathol. Exp. Neurol."
    },
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      "key": "e_1_3_1_24_2",
      "unstructured": "S. Kato et al. ibid. p. 1089."
    },
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      "key": "e_1_3_1_25_2",
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      "volume": "151",
      "author": "Kato S.",
      "year": "1997",
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      "journal-title": "Am. J. Pathol."
    },
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      "key": "e_1_3_1_26_2",
      "doi-asserted-by": "crossref",
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      "DOI": "10.1073/pnas.92.4.954",
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      "author": "Pardo C. A.",
      "year": "1995",
      "unstructured": "Pardo C. A., et al., Proc. Natl. Acad. Sci. U.S.A. 92, 954 (1995).",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
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      "key": "e_1_3_1_27_2",
      "doi-asserted-by": "crossref",
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      "volume": "346",
      "author": "Liochev S. I.",
      "year": "1997",
      "unstructured": "Liochev S. I., Chen L. L., Hallewell R. A., Fridovich I., Arch. Biochem. Biophys. 346, 263 (1997).",
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      "doi-asserted-by": "crossref",
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      "author": "Yim H. S.",
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      "unstructured": "Yim H. S., Kang J. H., Chock P. B., Stadtman E. R., Yim M. B., J. Biol. Chem. 272, 8861 (1997).",
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      "author": "Bruijn L.",
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    },
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      "author": "Ferrante R. J.",
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    },
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      "unstructured": "M. F. Beal et al. ibid. p. 646."
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      "author": "Singh R. J.",
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