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Epigenetic Mechanisms of Gene Regulation in Amyotrophic Lateral Sclerosis

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Neuroepigenomics in Aging and Disease

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

Abstract

Despite being clinically described 150 years ago, the mechanisms underlying amyotrophic lateral sclerosis (ALS) pathogenesis have not yet been fully understood. Studies in both animal models of ALS and human patients reveal a plethora of alterations such as increased glutamate-mediated excitotoxicity, redox stress, increased apoptosis, defective axonal transport, protein-misfolding events, mitochondrial impairment and sustained unregulated immune responses. Regardless of being sporadic or familiar ALS, the final outcome at the cellular level is the death of upper and lower motor neurons, and once diagnosed, ALS is typically lethal within the next 5 years. There are neither clear biomarkers nor therapeutic or disease-modifying treatments for ALS.

Accumulating evidence supports the concept that epigenetic-driven modifications, including altered chromatin remodelling events, RNA editing and non-coding RNA molecules, might shed light into the pathogenic mechanisms underlying sporadic/familiar ALS onset and/or severity to facilitate the identification of effective therapies, early diagnosis and potentially early-stage therapeutic interventions to increase the survival outcome of ALS patients.

Alba Jimenez-Pacheco and Jaime M. Franco contributed equally to this work.

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Acknowledgments

This work was supported by the following grants: PS09-2252 (to DP) from the Spanish Ministry of Economy (Instituto de Salud Carlos III) and co-funded by FEDER; P11-CTS8161 (to DP) from the Regional Ministry of Economy and PI13-575 (to SL) from the Regional Ministry of Health. MCG received support from an educational grant from PIF-University of Seville PhD programme. DEC received support from CONACYT postdoctoral programme (Gobierno de Mexico). We appreciate Jorge Abarca’s Reto4ELA and ELA Andalucia Foundation continuous support.

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Authors and Affiliations

  1. CABIMER, Andalusian Center for Molecular Biology and Regenerative Medicine, Av. Americo Vespucio s/n, 41092, Seville, Spain

    Alba Jimenez-Pacheco, Jaime M. Franco, Soledad Lopez, Maria Magdalena Leal-Lasarte, Diana E. Caballero-Hernandez, Marta Cejudo-Guillén & David Pozo

  2. Department of Medical Biochemistry, Molecular Biology and Immunology, University of Seville Medical School, Seville, Spain

    Alba Jimenez-Pacheco, Jaime M. Franco, Soledad Lopez, Marta Cejudo-Guillén & David Pozo

  3. Genomic Unit, Malaga Institute of Biomedical Research (IBIMA), Malaga, Spain

    Juan Miguel Gomez-Zumaquero

  4. School of Biological Sciences, Autonomous University of Nuevo Leon (UANL), Nuevo Leon, Mexico

    Diana E. Caballero-Hernandez

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

    Raul Delgado-Morales

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Jimenez-Pacheco, A. et al. (2017). Epigenetic Mechanisms of Gene Regulation in Amyotrophic Lateral Sclerosis. 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_14

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