Pcaf modulates polyglutamine pathology in a Drosophila model of Huntington's disease

Laszlo Bodai, Judit Pallos, Leslie Michels Thompson, J. Lawrence Marsh

Research output: Contribution to journalArticle

12 Citations (Scopus)


Huntingtin peptides with elongated polyglutamine domains, the root causes of Huntington's disease, hinder histone acetylation, which leads to transcriptional dysregulation. However, the range of acetyltransferases interacting with mutant Huntingtin has not been systematically evaluated. We used genetic interaction tests in Drosophila to determine whether specific acetyltransferases belonging to distinct protein families influence polyglutamine pathology. We found that flies expressing a mutant form of the Huntingtin protein (Httex1pQ93) exhibit reduced viability, which is further decreased by partial loss of Pcaf or nejire, while the tested MYST family acetyltransferases did not affect pathology. Reduced levels of Pcaf also led to the increased degeneration of photoreceptor neurons in the retina. Overexpression of Pcaf, however, was not sufficient to ameliorate these phenotypes, and the level of soluble Pcaf is unchanged in Httex1pQ93-expressing flies. Thus, our results indicate that while Pcaf has a significant impact on Huntington's disease pathology, therapeutic strategies aimed at elevating its levels are likely to be ineffective in ameliorating Huntington's disease pathology; however, strategies that aim to increase the specific activity of Pcaf remain to be tested.

Original languageEnglish
Pages (from-to)104-106
Number of pages3
JournalNeurodegenerative Diseases
Issue number2
Publication statusPublished - Feb 2012


  • Drosophila
  • Histone acetyltransferase
  • Huntington's disease
  • Nejire
  • Pcaf
  • Polyglutamine

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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