Dysfunction of the ubiquitin-proteasome system in multiple disease conditions: therapeutic approaches

Bioessays. 2008 Nov;30(11-12):1172-84. doi: 10.1002/bies.20852.


The ubiquitin-proteasome system (UPS) is the major proteolytic pathway that degrades intracellular proteins in a regulated manner. Deregulation of the UPS has been implicated in the pathogenesis of many neurodegenerative disorders like Alzheimer's disease, Parkinson's diseases, Huntington disease, Prion-like lethal disorders, in the pathogenesis of several genetic diseases including cystic fibrosis, Angelman's syndrome and Liddle syndrome and in many cancers. Multiple lines of evidence have already proved that UPS has the potential to be an exciting novel therapeutic target for the treatment of these diseases. Here I review how aberrant functions of various genes have implicated UPS in many human disorders including neurodegeneration and cancers. I also discuss the finding that some proteasome inhibitors possess a therapeutic potential as drugs against many such diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Models, Biological
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism
  • Protease Inhibitors / pharmacology
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Endopeptidase Complex / physiology*
  • Proteasome Inhibitors
  • Protein Denaturation
  • Protein Folding
  • Signal Transduction
  • Transcription, Genetic
  • Ubiquitin / chemistry
  • Ubiquitin / metabolism*
  • beta Catenin / metabolism


  • Protease Inhibitors
  • Proteasome Inhibitors
  • Ubiquitin
  • beta Catenin
  • Proteasome Endopeptidase Complex