title: Lack of evidence of monomer/misfolded superoxide dismutase-1 in sporadic amyotrophic lateral sclerosis.
abstract: OBJECTIVE
  In familial amyotrophic lateral sclerosis (fALS) harboring superoxide dismutase (SOD1) mutations (fALS1), SOD1 toxicity has been linked to its propensity to misfold and aggregate. It has recently been proposed that misfolded SOD1 may be causative of all types of ALS, including sporadic cases (sALS). In the present study, we have used a specific antibody to test for the presence of monomer/misfolded SOD1 in sALS.
  
  
  METHODS
  Sections from lumbar spinal cords of 5 fALS1 cases, 13 sALS cases, and 1 non-SOD1 fALS case were labeled immunocytochemically using SOD1-exposed-dimer-interface (SEDI) antibody, which we have previously validated as being specific for pathological monomer/misfolded forms of SOD1.
  
  
  RESULTS
  Monomer/misfolded SOD1 was detected with SEDI antibody in all 5 of the fALS1 cases, localizing predominantly to hyaline conglomerate inclusions, a specific pathological feature of fALS1. In contrast, monomer/misfolded SOD1 was not detected in any of the 13 sALS cases or in the non-SOD1 fALS cases. These results were confirmed by immunoprecipitation.
  
  
  CONCLUSIONS
  Although SEDI antibody does not necessarily label all misfolded forms of SOD1, these findings show a distinct difference between fALS1 and sALS, and do not support that monomer/misfolded SOD1 is a common disease entity linking all types of ALS. This is important to our understanding of ALS disease pathogenesis and to considerations of the applicability of using therapeutics that target misfolded SOD1 to non-SOD1-related cases. Ann Neurol 2009;66:75-80.
authors: Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
authors: Hsueh-Ning
authors: HN
authors: Liu
authors: Teresa
authors: T
authors: Sanelli
authors: Patrick
authors: P
authors: Horne
authors: Erik P
authors: EP
authors: Pioro
authors: Michael J
authors: MJ
authors: Strong
authors: Ekaterina
authors: E
authors: Rogaeva
authors: Juan
authors: J
authors: Bilbao
authors: Lorne
authors: L
authors: Zinman
authors: Janice
authors: J
authors: Robertson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D017510:Protein Folding; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1
chemical_list: C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1