Cystatin B and SOD1: protein–protein interaction and possible relation to neurodegeneration

Cell Mol Neurobiol. 2014 Mar;34(2):205-13. doi: 10.1007/s10571-013-0004-y.


Cystatin B (CSTB), an inhibitor of the cysteine proteases, belongs to the cathepsin family and it is known to interact with a number of proteins involved in cytoskeletal organization. CSTB has an intrinsic tendency to form aggregates depending on the redox environment. The gene encoding for CSTB is frequently mutated in association with the rare neurodegenerative condition progressive myoclonus epilepsy. Increased levels of CSTB have been observed in the spinal cord of transgenic mice modeling SOD1-linked familial amyotrophic lateral sclerosis, a fatal neurodegenerative disease affecting motoneurons. In the present study, we have investigated the relationship occurring between the expression of SOD1 and CSTB either wild-type or double-cysteine substitution mutant (Cys 3 and Cys 64). Whether or not there is a physical interaction between the two proteins was also investigated in overexpression experiments using a human neuroblastoma cell line and mouse-immortalized motoneurons. Here we report evidences for a reciprocal influence of CSTB and SOD1 at the gene expression level and for a direct interaction of the two proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line
  • Clone Cells
  • Cystatin B / genetics
  • Cystatin B / metabolism*
  • Gene Expression Regulation
  • Humans
  • Immunoprecipitation
  • Mice
  • Mutant Proteins / metabolism
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / pathology*
  • Protein Binding
  • Rats
  • Solubility
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Superoxide Dismutase-1


  • Mutant Proteins
  • SOD1 protein, human
  • Cystatin B
  • Sod1 protein, mouse
  • Sod1 protein, rat
  • Superoxide Dismutase
  • Superoxide Dismutase-1