Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila

@article{Steffan2001HistoneDI,
  title={Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila},
  author={Joan S. Steffan and L{\'a}szl{\'o} Bodai and Judit Pallos and Marnix Poelman and Alexander McCampbell and Barbara L. Apostol and A Kazantsev and Emily Schmidt and Ya-zhen Zhu and Marilee Greenwald and Riki Kurokawa and David E. Housman and George R. Jackson and J. Lawrence Marsh and Leslie M. Thompson},
  journal={Nature},
  year={2001},
  volume={413},
  pages={739-743}
}
Proteins with expanded polyglutamine repeats cause Huntington's disease and other neurodegenerative diseases. Transcriptional dysregulation and loss of function of transcriptional co-activator proteins have been implicated in the pathogenesis of these diseases. Huntington's disease is caused by expansion of a repeated sequence of the amino acid glutamine in the abnormal protein huntingtin (Htt). Here we show that the polyglutamine-containing domain of Htt, Htt exon 1 protein (Httex1p), directly… 
Histone deacetylase inhibitors reduce polyglutamine toxicity
TLDR
It is suggested that nuclear accumulation of polyglutamine can lead to altered protein acetylation in neurons and indicate a novel therapeutic strategy for polyglUTamine disease.
Histone deacetylase activity is retained in primary neurons expressing mutant huntingtin protein
Perturbation of histone acetyl‐transferase (HAT) activity is implicated in the pathology of polyglutamine diseases, and suppression of the counteracting histone deacetylase (HDAC) proteins has been
Disassociation of Histone Deacetylase-3 from Normal Huntingtin Underlies Mutant Huntingtin Neurotoxicity
TLDR
It is shown that Htt is a neuroprotective protein in both HD-related and unrelated model systems and identifies HDAC3 as an essential player in mutant Htt-induced neurodegeneration.
Differential Contributions of Caenorhabditis elegans Histone Deacetylases to Huntingtin Polyglutamine Toxicity
TLDR
It is suggested that polyglutamine expansions perturb transcription of CREB/CBP targets and that specific targeting of HDACs will be useful in reducing associated neurodegeneration.
Aberrant histone acetylation, altered transcription, and retinal degeneration in a Drosophila model of polyglutamine disease are rescued by CREB-binding protein.
TLDR
It is demonstrated that polyglutamine-induced neurodegeneration is accompanied by a defect in histone acetylation and a substantial alteration in the transcription profile, and that transcriptional dysregulation is an important part of the pathogenesis of polyglutanism.
Histone deacetylase inhibitors as therapeutics for polyglutamine disorders
TLDR
The potential therapeutic pathways through which histone deacetylase inhibitors might act to correct the aberrant transcription observed in Huntington's disease and other polyglutamine repeat diseases are discussed.
Altered Histone Monoubiquitylation Mediated by Mutant Huntingtin Induces Transcriptional Dysregulation
TLDR
This is the first report to demonstrate hPRC1L as a huntingtin-interacting histone modifying complex and a crucial role for histone monoubiquitylation in mammalian brain gene expression, which broadens the understanding of histone code.
Selective inhibition of histone deacetylase 1 and 3 improves motor phenotype and alleviates transcriptional dysregulation in Huntington’s disease mice
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease characterized by a late clinical onset of psychiatric, cognitive, and motor symptoms. Transcriptional dysregulation is an
Genetic modulation of polyglutamine toxicity by protein conjugation pathways in Drosophila.
TLDR
The data suggest that post-translational protein modification, including the ubiquitin/proteasome and the SUMO-1 pathways, modulate poly(Q) pathogenesis.
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