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Citation
Bodai, L., Pallos, J., Thompson, L.M., Marsh, J.L. (2012). Pcaf Modulates Polyglutamine Pathology in a Drosophila Model of Huntington's Disease.  Neurodegener. Dis. 9(2): 104--106.
FlyBase ID
FBrf0217401
Publication Type
Research paper
Abstract

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.

PubMed ID
PubMed Central ID
PMC3304510 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Neurodegener. Dis.
    Title
    Neuro-degenerative Diseases
    Publication Year
    2004-
    ISBN/ISSN
    1660-2854 1660-2862
    Data From Reference
    Aberrations (2)
    Alleles (7)
    Genes (7)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (1)
    Experimental Tools (1)
    Transgenic Constructs (2)