Neurotherapeutics

, Volume 10, Issue 4, pp 664–676

Epigenetic Mechanisms of Neurodegeneration in Huntington’s Disease

  • Junghee Lee
  • Yu Jin Hwang
  • Ki Yoon Kim
  • Neil W. Kowall
  • Hoon Ryu
Review

DOI: 10.1007/s13311-013-0206-5

Cite this article as:
Lee, J., Hwang, Y.J., Kim, K.Y. et al. Neurotherapeutics (2013) 10: 664. doi:10.1007/s13311-013-0206-5

Abstract

Huntington’s disease (HD) is an incurable and fatal hereditary neurodegenerative disorder of mid-life onset characterized by chorea, emotional distress, and progressive cognitive decline. HD is caused by an expansion of CAG repeats coding for glutamine (Q) in exon 1 of the huntingtin gene. Recent studies suggest that epigenetic modifications may play a key role in HD pathogenesis. Alterations of the epigenetic “histone code” lead to chromatin remodeling and deregulation of neuronal gene transcription that are prominently linked to HD pathogenesis. Furthermore, specific noncoding RNAs and microRNAs are associated with neuronal damage in HD. In this review, we discuss how DNA methylation, post-translational modifications of histone, and noncoding RNA function are affected and involved in HD pathogenesis. In addition, we summarize the therapeutic effects of histone deacetylase inhibitors and DNA binding drugs on epigenetic modifications and neuropathological sequelae in HD. Our understanding of the role of these epigenetic mechanisms may lead to the identification of novel biological markers and new therapeutic targets to treat HD.

Keywords

DNA methylation Histone code Chromatin remodeling Noncoding RNA microRNA Huntington’s disease Therapeutics 

Supplementary material

13311_2013_206_MOESM1_ESM.pdf (499 kb)
ESM 1(PDF 499 kb)

Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2013

Authors and Affiliations

  • Junghee Lee
    • 1
    • 2
  • Yu Jin Hwang
    • 3
  • Ki Yoon Kim
    • 3
  • Neil W. Kowall
    • 1
    • 2
  • Hoon Ryu
    • 1
    • 2
    • 3
  1. 1.Boston University Alzheimer’s Disease Center and Department of Neurology, Boston University School of MedicineBostonUSA
  2. 2.VA Boston Healthcare SystemBostonUSA
  3. 3.WCU Neurocytomics Group, Department of Biomedical SciencesSeoul National University Graduate SchoolSeoulSouth Korea

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