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Epigenetics of Huntington’s Disease

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Neuroepigenomics in Aging and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((PMISB,volume 978))

Abstract

Huntington’s disease (HD) is a genetic, fatal autosomal dominant neurodegenerative disorder typically occurring in midlife with symptoms ranging from chorea, to dementia, to personality disturbances (Philos Trans R Soc Lond Ser B Biol Sci 354:957–961, 1999). HD is inherited in a dominant fashion, and the underlying mutation in all cases is a CAG trinucleotide repeat expansion within exon 1 of the HD gene (Cell 72:971–983, 1993). The expanded CAG repeat, translated into a lengthened glutamine tract at the amino terminus of the huntingtin protein, affects its structural properties and functional activities. The effects are pleiotropic, as huntingtin is broadly expressed in different cellular compartments (i.e., cytosol, nucleus, mitochondria) as well as in all cell types of the body at all developmental stages, such that HD pathogenesis likely starts at conception and is a lifelong process (Front Neurosci 9:509, 2015). The rate-limiting mechanism(s) of neurodegeneration in HD still remains elusive: many different processes are commonly disrupted in HD cell lines and animal models, as well as in HD patient cells (Eur J Neurosci 27:2803–2820, 2008); however, epigenetic-chromatin deregulation, as determined by the analysis of DNA methylation, histone modifications, and noncoding RNAs, has now become a prevailing feature. Thus, the overarching goal of this chapter is to discuss the current status of the literature, reviewing how an aberrant epigenetic landscape can contribute to altered gene expression and neuronal dysfunction in HD.

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Authors and Affiliations

  1. The NeuroEpigenetics Laboratory, Centre for Integrative Biology, University of Trento, Via Sommarive 9, 38123, Povo (TN), Italy

    Silvia Bassi Ph.D., Takshashila Tripathi Ph.D., Alan Monziani, Francesca Di Leva Ph.D. & Marta Biagioli Ph.D.

Authors
  1. Silvia Bassi Ph.D.
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  2. Takshashila Tripathi Ph.D.
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  3. Alan Monziani
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  4. Francesca Di Leva Ph.D.
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  5. Marta Biagioli Ph.D.
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Corresponding author

Correspondence to Marta Biagioli Ph.D. .

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Editors and Affiliations

  1. Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), CATALONIA, Spain

    Raul Delgado-Morales

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Bassi, S., Tripathi, T., Monziani, A., Di Leva, F., Biagioli, M. (2017). Epigenetics of Huntington’s Disease. In: Delgado-Morales, R. (eds) Neuroepigenomics in Aging and Disease. Advances in Experimental Medicine and Biology(), vol 978. Springer, Cham. https://doi.org/10.1007/978-3-319-53889-1_15

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