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Epigenetic Mechanisms of Neurodegeneration in Huntington’s Disease

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  • Published:
Neurotherapeutics

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.

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Acknowledgments

This study was supported by NIH NS 067283–02 (H.R.), WCU Neurocytomics Program Grant (800–20080848) (H.R.), and SRC Grant (2010-0029-403) (H.R.) from National Research Foundation, and Flagship Grant (H.R.) from KIST.

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Authors and Affiliations

  1. Boston University Alzheimer’s Disease Center and Department of Neurology, Boston University School of Medicine, Boston, MA, 02118, USA

    Junghee Lee, Neil W. Kowall & Hoon Ryu

  2. VA Boston Healthcare System, Boston, MA, 02130, USA

    Junghee Lee, Neil W. Kowall & Hoon Ryu

  3. WCU Neurocytomics Group, Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, 110-799, South Korea

    Yu Jin Hwang, Ki Yoon Kim & Hoon Ryu

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  1. Junghee Lee
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  2. Yu Jin Hwang
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  3. Ki Yoon Kim
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  4. Neil W. Kowall
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  5. Hoon Ryu
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Correspondence to Hoon Ryu.

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Lee, J., Hwang, Y.J., Kim, K.Y. et al. Epigenetic Mechanisms of Neurodegeneration in Huntington’s Disease. Neurotherapeutics 10, 664–676 (2013). https://doi.org/10.1007/s13311-013-0206-5

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