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An Epigenetic Spin to ALS and FTD

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Book cover RNA Metabolism in Neurodegenerative Diseases

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 20))

Abstract

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two devastating and lethal neurodegenerative diseases seen comorbidly in up to 15% of patients. Despite several decades of research, no effective treatment or disease-modifying strategies have been developed. We now understand more than before about the genetics and biology behind ALS and FTD, but the genetic etiology for the majority of patients is still unknown and the phenotypic variability observed across patients, even those carrying the same mutation, is enigmatic. Additionally, susceptibility factors leading to neuronal vulnerability in specific central nervous system regions involved in disease are yet to be identified. As the inherited but dynamic epigenome acts as a cell-specific interface between the inherited fixed genome and both cell-intrinsic mechanisms and environmental input, adaptive epigenetic changes might contribute to the ALS/FTD aspects we still struggle to comprehend. This chapter summarizes our current understanding of basic epigenetic mechanisms, how they relate to ALS and FTD, and their potential as therapeutic targets. A clear understanding of the biological mechanisms driving these two currently incurable diseases is urgent—well-needed therapeutic strategies need to be developed soon. Disease-specific epigenetic changes have already been observed in patients and these might be central to this endeavor.

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Acknowledgments

We would like to thank Dr. Tamas Ordog, Director of the Epigenomics Translational Program at Mayo Clinic Center for Individualized Medicine for reviewing and providing critical input for this manuscript.

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Author notes

  1. Mark T. W. Ebbert and Rebecca J. Lank contributed equally to this work.

Authors and Affiliations

  1. Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA

    Mark T. W. Ebbert & Veronique V. Belzil

  2. Department of Neurology, University of Michigan, Ann Arbor, MI, USA

    Rebecca J. Lank

  3. Department of Neurology and Neurosurgery, McGill University, Montreal, QC, Canada

    Veronique V. Belzil

Authors
  1. Mark T. W. Ebbert
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  2. Rebecca J. Lank
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  3. Veronique V. Belzil
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Corresponding author

Correspondence to Veronique V. Belzil .

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Editors and Affiliations

  1. Department of Neurobiology and Neurology, Dignityhealth St. Joseph’s Hospital, Barrow Neurological Institute, Phoenix, Arizona, USA

    Rita Sattler

  2. Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Christopher J. Donnelly

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Ebbert, M.T.W., Lank, R.J., Belzil, V.V. (2018). An Epigenetic Spin to ALS and FTD. In: Sattler, R., Donnelly, C. (eds) RNA Metabolism in Neurodegenerative Diseases. Advances in Neurobiology, vol 20. Springer, Cham. https://doi.org/10.1007/978-3-319-89689-2_1

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