GRP78 counteracts cell death and protein aggregation caused by mutant huntingtin proteins

Neurosci Lett. 2012 May 16;516(2):182-7. doi: 10.1016/j.neulet.2012.03.074. Epub 2012 Apr 2.

Abstract

The ER-localized chaperone glucose-regulated protein (GRP78) protects neurons against excitotoxicity and apoptosis. Here we show that overexpressing GRP78 protects N2a cells against mutant huntingtin proteins, reduces formation of mutant huntingtin aggregates, inhibits caspase-12 activation and blocks cell death. Our data suggest that GRP78 may be a promising therapeutic target for the treatment of Huntington's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cell Line
  • Endoplasmic Reticulum / metabolism
  • Endoplasmic Reticulum / pathology
  • Endoplasmic Reticulum Stress / physiology
  • Heat-Shock Proteins / metabolism*
  • Huntingtin Protein
  • Huntington Disease / genetics
  • Huntington Disease / metabolism*
  • Immunoblotting
  • Mice
  • Microscopy, Confocal
  • Mutant Proteins / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA Interference
  • Transfection

Substances

  • Heat-Shock Proteins
  • Htt protein, mouse
  • Huntingtin Protein
  • Mutant Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • molecular chaperone GRP78