Autophagy for the avoidance of neurodegeneration

Genes Dev. 2009 Oct 1;23(19):2253-9. doi: 10.1101/gad.1858009.

Abstract

Cellular defense mechanisms, including the unfolded protein response (UPR) and autophagy, attempt to resolve toxic protein aggregates, which are common denominators of neurodegenerative diseases. In this issue of Genes & Development, Hetz and colleagues (pp. 2294-2306) surprisingly show that inhibition of the UPR by knockout of XBP-1 causes a massive increase in autophagy, enhances clearance of superoxide dismutase 1 (SOD1) aggregates, and delays the development of amyotrophic lateral sclerosis. These findings suggest the existence of a homeostatic-if not hormetic-balance between distinct cellular defense mechanisms.

Publication types

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

MeSH terms

  • Aging / physiology
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Animals
  • Autophagy / genetics
  • Autophagy / physiology*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Gene Knockout Techniques
  • Homeostasis / physiology
  • Humans
  • Neurons / pathology
  • Neurons / physiology*
  • Regulatory Factor X Transcription Factors
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • X-Box Binding Protein 1

Substances

  • DNA-Binding Proteins
  • Regulatory Factor X Transcription Factors
  • SOD1 protein, human
  • Transcription Factors
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • Superoxide Dismutase
  • Superoxide Dismutase-1