Autophagy and the ubiquitin-proteasome system: collaborators in neuroprotection

Biochim Biophys Acta. 2008 Dec;1782(12):691-9. doi: 10.1016/j.bbadis.2008.10.002. Epub 2008 Oct 10.


Protein degradation is an essential cellular function that, when dysregulated or impaired, can lead to a wide variety of disease states. The two major intracellular protein degradation systems are the ubiquitin-proteasome system (UPS) and autophagy, a catabolic process that involves delivery of cellular components to the lysosome for degradation. While the UPS has garnered much attention as it relates to neurodegenerative disease, important links between autophagy and neurodegeneration have also become evident. Furthermore, recent studies have revealed interaction between the UPS and autophagy, suggesting a coordinated and complementary relationship between these degradation systems that becomes critical in times of cellular stress. Here we describe autophagy and review evidence implicating this system as an important player in the pathogenesis of neurodegenerative disease. We discuss the role of autophagy in neurodegeneration and review its neuroprotective functions as revealed by experimental manipulation in disease models. Finally, we explore potential parallels and connections between autophagy and the UPS, highlighting their collaborative roles in protecting against neurodegenerative disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagy / physiology*
  • Humans
  • Neurodegenerative Diseases / physiopathology*
  • Neurodegenerative Diseases / therapy
  • Neuroprotective Agents / therapeutic use*
  • Proteasome Endopeptidase Complex / metabolism*
  • Ubiquitin / metabolism*


  • Neuroprotective Agents
  • Ubiquitin
  • Proteasome Endopeptidase Complex