Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington's disease Academic Article uri icon


MeSH Major

  • Histone Deacetylase Inhibitors
  • Huntington Disease
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Nuclear Proteins
  • Phenylbutyrates


  • Huntington's disease (HD) is caused by an expansion of exonic CAG triplet repeats in the gene encoding the huntingtin protein (Htt), however, the means by which neurodegeneration occurs remains obscure. There is evidence that mutant Htt interacts with transcription factors leading to reduced histone acetylation. We report that administration of the histone deacetylase inhibitor phenylbutyrate after onset of symptoms in a transgenic mouse model of HD significantly extends survival and attenuates both gross brain and neuronal atrophy. Administration of phenylbutyrate increased brain histone acetylation and decreased histone methylation levels as assessed by both immunocytochemistry and Western blots. Phenylbutyrate increased mRNA for components of the ubiquitin-proteosomal pathway and down-regulated caspases implicated in apoptotic cell death, and active caspase 3 immunoreactivity in the striatum. These results show that administration of phenylbutyrate, at doses that are well tolerated in man, exerts significant neuroprotective effects in a transgenic mouse model of HD, and therefore represents a very promising therapeutic approach for HD.

publication date

  • January 7, 2005



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1074/jbc.M410210200

PubMed ID

  • 15494404

Additional Document Info

start page

  • 556

end page

  • 63


  • 280


  • 1