Mutant SOD1 causes motor neuron disease independent of copper chaperone-mediated copper loading

Jamuna R. Subramaniam, W. Ernest Lyons, Jian Liu, Thomas B. Bartnikas, Jeffrey D Rothstein, Donald L. Price, Don W. Cleveland, Jonathan D. Gitlin, Philip Chun Wong

Research output: Contribution to journalArticle

Abstract

Copper-mediated oxidative damage is proposed to play a critical role in the pathogenesis of Cu/Zn superoxide dismutase (SOD1)-linked familial amyotrophic lateral sclerosis (FALS). We tested this hypothesis by ablating the gene encoding the copper chaperone for SOD1 (CCS) in a series of FALS-linked SOD1 mutant mice. Metabolic 64Cu labeling in SOD1-mutant mice lacking the CCS showed that the incorporation of copper into mutant SOD1 was significantly diminished in the absence of CCS. Motor neurons in CCS-/- mice showed increased rate of death after facial nerve axotomy, a response documented for SOD1-/- mice. Thus, CCS is necessary for the efficient incorporation of copper into SOD1 in motor neurons. Although the absence of CCS led to a significant reduction in the amount of copper-loaded mutant SOD1, however, it did not modify the onset and progression of motor neuron disease in SOD1-mutant mice. Hence, CCS-dependent copper loading of mutant SOD1 plays no role in the pathogenesis of motor neuron disease in these mouse models.

Original languageEnglish (US)
Pages (from-to)301-307
Number of pages7
JournalNature Neuroscience
Volume5
Issue number4
DOIs
StatePublished - 2002

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Motor Neuron Disease
Copper
Motor Neurons
Axotomy
Facial Nerve

ASJC Scopus subject areas

  • Neuroscience(all)

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Mutant SOD1 causes motor neuron disease independent of copper chaperone-mediated copper loading. / Subramaniam, Jamuna R.; Lyons, W. Ernest; Liu, Jian; Bartnikas, Thomas B.; Rothstein, Jeffrey D; Price, Donald L.; Cleveland, Don W.; Gitlin, Jonathan D.; Wong, Philip Chun.

In: Nature Neuroscience, Vol. 5, No. 4, 2002, p. 301-307.

Research output: Contribution to journalArticle

Subramaniam, JR, Lyons, WE, Liu, J, Bartnikas, TB, Rothstein, JD, Price, DL, Cleveland, DW, Gitlin, JD & Wong, PC 2002, 'Mutant SOD1 causes motor neuron disease independent of copper chaperone-mediated copper loading', Nature Neuroscience, vol. 5, no. 4, pp. 301-307. https://doi.org/10.1038/nn823
Subramaniam, Jamuna R. ; Lyons, W. Ernest ; Liu, Jian ; Bartnikas, Thomas B. ; Rothstein, Jeffrey D ; Price, Donald L. ; Cleveland, Don W. ; Gitlin, Jonathan D. ; Wong, Philip Chun. / Mutant SOD1 causes motor neuron disease independent of copper chaperone-mediated copper loading. In: Nature Neuroscience. 2002 ; Vol. 5, No. 4. pp. 301-307.
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