Chaperone networks: tipping the balance in protein folding diseases

Neurobiol Dis. 2010 Oct;40(1):12-20. doi: 10.1016/j.nbd.2010.05.007. Epub 2010 May 21.

Abstract

Adult-onset neurodegeneration and other protein conformational diseases are associated with the appearance, persistence, and accumulation of misfolded and aggregation-prone proteins. To protect the proteome from long-term damage, the cell expresses a highly integrated protein homeostasis (proteostasis) machinery to ensure that proteins are properly expressed, folded, and cleared, and to recognize damaged proteins. Molecular chaperones have a central role in proteostasis as they have been shown to be essential to prevent the accumulation of alternate folded proteotoxic states as occurs in protein conformation diseases exemplified by neurodegeneration. Studies using invertebrate models expressing proteins associated with Huntington's disease, Alzheimer's disease, ALS, and Parkinson's disease have provided insights into the genetic networks and stress signaling pathways that regulate the proteostasis machinery to prevent cellular dysfunction, tissue pathology, and organismal failure. These events appear to be further amplified by aging and provide evidence that age-related failures in proteostasis may be a common element in many diseases.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / chemistry
  • Caenorhabditis elegans / genetics
  • Gene Regulatory Networks / physiology*
  • Humans
  • Molecular Chaperones / chemistry*
  • Molecular Chaperones / genetics*
  • Protein Conformation
  • Protein Folding*
  • Proteostasis Deficiencies / genetics*
  • Proteostasis Deficiencies / metabolism*

Substances

  • Molecular Chaperones