The ubiquitin proteasome system in neurodegenerative diseases: Culprit, accomplice or victim?

F. J. A. Dennissen*, N. Kholod, F. W. van Leeuwen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


A shared hallmark for many neurodegenerative disorders is the accumulation of toxic protein species which is assumed to be the cause for these diseases. Since the ubiquitin proteasome system (UPS) is the most important pathway for selective protein degradation it is likely that it is involved in the aetiology neurodegenerative disorders. Indeed, impairment of the UPS has been reported to occur during neurodegeneration. Although accumulation of toxic protein species (amyloid beta) are in turn known to impair the UPS the relationship is not necessarily causal. We provide an overview of the most recent insights in the roles the UPS plays in protein degradation and other processes. Additionally, we discuss the role of the UPS in clearance of the toxic proteins known to accumulate in the hallmarks of neurodegenerative diseases. The present paper will focus on critically reviewing the involvement of the UPS in specific neurodegenerative diseases and will discuss if UPS impairment is a cause, a consequence or both of the disease.
Original languageEnglish
Pages (from-to)190-207
JournalProgress in Neurobiology
Issue number2
Publication statusPublished - Feb 2012


  • Neurodegenerative diseases
  • Ubiquitin proteasome system
  • Alzheimer's disease
  • Parkinson's disease
  • Huntington's disease
  • Frontotemporal dementia
  • Amyotrophic lateral sclerosis
  • Ubiquitin
  • Protein degradation
  • Ubiquitin-like proteins

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