The roles of intracellular protein-degradation pathways in neurodegeneration

Nature. 2006 Oct 19;443(7113):780-6. doi: 10.1038/nature05291.

Abstract

Many late-onset neurodegenerative diseases, including Parkinson's disease and Huntington's disease, are associated with the formation of intracellular aggregates by toxic proteins. It is therefore crucial to understand the factors that regulate the steady-state levels of these 'toxins', at both the synthetic and degradation stages. The degradation pathways acting on such aggregate-prone cytosolic proteins include the ubiquitin-proteasome system and macroautophagy. Dysfunction of the ubiquitin-proteasome or macroautophagy pathways might contribute to the pathology of various neurodegenerative conditions. However, enhancing macroautophagy with drugs such as rapamycin could offer a tractable therapeutic strategy for a number of these diseases.

Publication types

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

MeSH terms

  • Animals
  • Autophagy* / drug effects
  • Humans
  • Huntingtin Protein
  • Lysosomes / metabolism
  • Nerve Tissue Proteins / metabolism
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism*
  • Nuclear Proteins / metabolism
  • Proteasome Endopeptidase Complex / metabolism*
  • Ubiquitin / metabolism

Substances

  • HTT protein, human
  • Huntingtin Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Ubiquitin
  • Proteasome Endopeptidase Complex