Protective roles for induction of autophagy in multiple proteinopathies

Autophagy. 2006 Jul-Sep;2(3):224-5. doi: 10.4161/auto.2696. Epub 2006 Jul 10.

Abstract

Many late-onset neurodegenerative diseases, including Parkinson's disease, tauopathies, Huntington's disease and forms of spinocerebellar ataxia, are caused by aggregate-prone proteins. Previously we showed that mutant huntingtin is an autophagy substrate and that autophagy induction reduced soluble and aggregated huntingtin levels and attenuated its toxicity in cell, fly and mouse models of disease. We have recently shown in cell and fly models that autophagy induction may have general protective effects across a range of diseases caused by aggregate-prone intracellular proteins. First, we showed that this strategy reduces the levels of the primary toxin, the aggregate-prone mutant protein. Second, our recent work suggests that autophagy induction may have additional cytoprotective effects by protecting cells against a range of subsequent pro-apoptotic insults.

Publication types

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

MeSH terms

  • Animals
  • Autophagy* / drug effects
  • Autophagy* / physiology
  • Cytoprotection / drug effects*
  • Cytoprotection / physiology
  • Models, Biological
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / pathology*
  • Protein Biosynthesis / drug effects*
  • Sirolimus / pharmacology

Substances

  • Sirolimus