[Polyglutamine-expanded ataxin-3 is degraded by autophagy]

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2010 Feb;27(1):23-8. doi: 10.3760/cma.j.issn.1003-9406.2010.01.005.
[Article in Chinese]

Abstract

Objective: To investigate the role of autophagy on the pathogenesis of spinocerebellar ataxia 3/Machado-Joseph disease (SCA3/MJD).

Methods: HEK293 cells expressing polyglutamine-expanded ataxin-3 were used as cell model for SCA3/MJD. The level of polyglutamine-expanded ataxin-3 was detected after cells were treated with different inhibitors or inducer of autophagy.

Results: Inhibition of autophagy increased aggregate formation and cell death in HEK293 cells expressing mutated ataxin-3, and vice versa.

Conclusion: The data suggested that autophagy is involved in the degradation of mutant ataxin-3, resulting in a decrease in the proportions of aggregate-containing cells and cell death in HEK293 cells expressing polyglutamine-expanded ataxin-3. It is possible that autophagy may be applied as a potential therapeutic approach for SCA3/MJD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxin-3
  • Autophagy*
  • Cell Line
  • Humans
  • Machado-Joseph Disease / genetics
  • Machado-Joseph Disease / metabolism*
  • Machado-Joseph Disease / physiopathology*
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Peptides / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*

Substances

  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Peptides
  • Repressor Proteins
  • polyglutamine
  • ATXN3 protein, human
  • Ataxin-3