Brain CHIP: removing the culprits in neurodegenerative disease

Trends Mol Med. 2007 Jan;13(1):32-8. doi: 10.1016/j.molmed.2006.11.003. Epub 2006 Nov 28.


A factor that is common to the most-frequent neurodegenerative diseases is the accumulation of abnormal proteins that are associated with cellular dysfunction. Contrary to years of speculation, recent evidence suggests that soluble intermediates--not the visible pathological aggregates associated with disease--are the cause of neurotoxicity. These findings suggest that aggregate formation might be an adaptive stress response that is facilitated by neuronal protein triage molecules. In particular, the molecular co-chaperone CHIP (C terminus of HSC70-interacting protein) has been linked to several of these disorders, serving as a crucial catalyst for the ubiquitination of several heat shock protein (HSP)70 client proteins that are involved in neurodegenerative disease. Therefore, understanding the mechanisms that are involved in CHIP-mediated protein trafficking might provide invaluable clues to neuronal function, both in normal and diseased conditions.

Publication types

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

MeSH terms

  • Age Factors
  • HSP70 Heat-Shock Proteins / metabolism
  • Humans
  • Models, Biological*
  • Molecular Chaperones / metabolism*
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / physiopathology
  • Protein Transport / physiology
  • Ubiquitin-Protein Ligases / metabolism*


  • HSP70 Heat-Shock Proteins
  • Molecular Chaperones
  • STUB1 protein, human
  • Ubiquitin-Protein Ligases