No correlation between aggregates of Cu/Zn superoxide dismutase and cell death in familial amyotrophic lateral sclerosis

J Neurochem. 2002 Sep;82(5):1229-38. doi: 10.1046/j.1471-4159.2002.01056.x.


Aggregates of Cu/Zn superoxide dismutase (SOD) have been demonstrated in familial amyotrophic lateral sclerosis (FALS) and other neurodegenerative diseases; however, their role in disease pathogenesis is unclear. In this study, we investigated the presence of SOD aggregates in nerve growth factor (NGF)-differentiated PC12 cells and cell viability following: (i) transduction with replication-deficient recombinant adenoviruses (AdVs) expressing wild-type SOD (SODWT) or mutant SOD (SODMT, V148G or A4V); (ii) transfection of yellow fluorescent protein-tagged SODWT (SODWT-YFP) or SODMT (SODA4V-YFP, SODV148G-YFP). SOD aggregates were more prominent in cells following transduction of AdSODMT than AdSODWT and following treatment with H2O2, suggesting that mutant SOD leads to oxidation of cellular components. In addition, cells expressing SODMT-YFP yielded SOD aggregates that were significantly larger and more frequent than SOD aggregates in cells expressing SODWT-YFP. Proteasome inhibitors, but not cathepsin B inhibitors, increased aggregate formation but did not increase cell death. In addition, treatments that increased cell viability did not significantly decrease SOD aggregates. Taken together, our data demonstrate that there is no association between SOD aggregates and cell death in FALS.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Substitution
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / metabolism*
  • Animals
  • Cathepsin B / antagonists & inhibitors
  • Cell Death
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cysteine Endopeptidases
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Luminescent Proteins / genetics
  • Macromolecular Substances
  • Multienzyme Complexes / antagonists & inhibitors
  • Mutation
  • Nerve Growth Factor / pharmacology
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Oxidants / pharmacology
  • Oxidative Stress / drug effects
  • PC12 Cells
  • Proteasome Endopeptidase Complex
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Transduction, Genetic


  • Enzyme Inhibitors
  • Luminescent Proteins
  • Macromolecular Substances
  • Multienzyme Complexes
  • Oxidants
  • Recombinant Fusion Proteins
  • Nerve Growth Factor
  • Hydrogen Peroxide
  • Superoxide Dismutase
  • Cysteine Endopeptidases
  • Cathepsin B
  • Proteasome Endopeptidase Complex