Ubiquitin, the proteasome and protein degradation in neuronal function and dysfunction

Nat Rev Neurosci. 2008 Nov;9(11):826-38. doi: 10.1038/nrn2499.


Eukaryotic protein degradation by the proteasome and the lysosome is a dynamic and complex process in which ubiquitin has a key regulatory role. The distinctive morphology of the postmitotic neuron creates unique challenges for protein degradation systems with respect to cell-surface protein turnover and substrate delivery to proteolytic machineries that are required for both synaptic plasticity and self-renewal. Moreover, the discovery of ubiquitin-positive protein aggregates in a wide spectrum of neurodegenerative diseases underlines the importance and vulnerability of the degradative system in neurons. In this article, we discuss the molecular mechanism of protein degradation in the neuron with respect to both its function and its dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Neurons / physiology*
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteasome Endopeptidase Complex / physiology
  • Ubiquitin / metabolism*
  • Ubiquitin / physiology


  • Ubiquitin
  • Proteasome Endopeptidase Complex