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Fractionation for Resolution of Soluble and Insoluble Huntingtin Species
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Fractionation for Resolution of Soluble and Insoluble Huntingtin Species

Published on: February 27, 2018

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Nucleolar dysfunction in Huntington's disease

Junghee Lee1, Yu Jin Hwang2, Hyun Ryu3

  • 1VA Boston Healthcare System, Boston, MA 02130, USA; Boston University, Alzheimer's Disease Center, Department of Neurology, Boston University School of Medicine, Boston, MA 02118, USA.

Biochimica Et Biophysica Acta
|November 5, 2013
PubMed

Insights

Huntington's disease involves genetic mutations affecting neuronal function. This review explores how epigenetic modifications in the nucleolus, specifically involving upstream binding factor (UBF), may offer new therapeutic targets for this neurodegenerative disorder.

Area of Science:

  • Neuroscience
  • Genetics
  • Epigenetics

Background:

  • Huntington's disease (HD) is a fatal neurodegenerative disorder caused by CAG repeat expansion in the huntingtin gene.
  • The precise mechanisms leading to selective medium spiny neuron loss in HD remain unclear.
  • Emerging evidence links nucleolar stress and dysfunction to HD pathogenesis, including deregulation of ribosomal DNA (rDNA) transcription.

Purpose of the Study:

  • To review the role of nucleolar stress and epigenetic modifications in Huntington's disease.
  • To discuss the impact of post-translational modifications on upstream binding factor (UBF) and rDNA transcription in HD.

Main Methods:

  • Literature review focusing on nucleolar function, epigenetic regulation, and Huntington's disease.
  • Analysis of the interplay between histone acetyltransferase, histone methyltransferase, and UBF in rDNA transcription.
  • Examination of the link between nucleolar alterations and neuronal damage in HD.

Main Results:

  • Mutant huntingtin may induce nucleolar stress, affecting rDNA transcription.
  • Epigenetic modifications, particularly those involving UBF, are implicated in the nucleolar dysfunction observed in HD.
  • Histone acetyltransferase and histone methyltransferase activities influence UBF post-translational modifications and rDNA transcription.

Conclusions:

  • Understanding the epigenetic modulation of UBF-dependent rDNA transcription in the nucleolus is crucial for HD research.
  • This knowledge may lead to the identification of novel pathological markers for HD.
  • Targeting nucleolar epigenetic pathways presents a potential therapeutic strategy for Huntington's disease.

Keywords:
Acetylation and methylationEpigeneticsHuntington's diseaseNucleolusUpstream binding factor (UBF)rDNA transcription

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