Misfolded superoxide dismutase-1 in CSF from amyotrophic lateral sclerosis patients

J Neurochem. 2011 Apr;117(1):91-9. doi: 10.1111/j.1471-4159.2011.07177.x. Epub 2011 Feb 9.


Several of the superoxide dismutase-1 (SOD1) mutations linked to amyotrophic lateral sclerosis (ALS) lead to synthesis of structurally defective molecules, suggesting that any cytotoxic conformational species common for all mutations should be misfolded. SOD1 can be secreted and evidence from ALS model systems suggests that extracellular SOD1 may be involved in cytotoxicity. Three ELISAs specifically reacting with different sequence segments in misfolded SOD1 species were used for analysis of CSF from 38 neurological controls and from 96 ALS patients, 57 of whom were sporadic cases and 39 familial, including 22 patients carrying SOD1 mutations. Misfolded SOD1 was found in all samples. There were, however, no significant differences between patients with and without mutations, and between all the ALS patients and the controls. The estimated concentration of misfolded SOD1 in the interstitium of the CNS is a 1000 times lower than that required for appreciable cytotoxicity in model systems. The results argue against a direct cytotoxic role of extracellular misfolded SOD1 in ALS. Misfolded SOD1 in CSF cannot be used as a biomarker of ALS in patients with and without mutations in the enzyme.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Amyotrophic Lateral Sclerosis / cerebrospinal fluid*
  • Amyotrophic Lateral Sclerosis / enzymology*
  • Amyotrophic Lateral Sclerosis / genetics
  • Animals
  • Biomarkers / cerebrospinal fluid
  • Contraindications
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Middle Aged
  • Molecular Sequence Data
  • Mutation / genetics
  • Protein Folding*
  • Superoxide Dismutase / cerebrospinal fluid*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase-1


  • Biomarkers
  • SOD1 protein, human
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1