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Published in: Acta Neuropathologica 4/2016

01-10-2016 | Review

ALS and FTD: an epigenetic perspective

Authors: Veronique V. Belzil, Rebecca B. Katzman, Leonard Petrucelli

Published in: Acta Neuropathologica | Issue 4/2016

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Abstract

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two fatal neurodegenerative diseases seen in comorbidity in up to 50 % of cases. Despite tremendous efforts over the last two decades, no biomarkers or effective therapeutics have been identified to prevent, decelerate, or stop neuronal death in patients. While the identification of multiple mutations in more than two dozen genes elucidated the involvement of several mechanisms in the pathogenesis of both diseases, identifying the hexanucleotide repeat expansion in C9orf72, the most common genetic abnormality in ALS and FTD, opened the door to the discovery of several novel pathogenic biological routes, including chromatin remodeling and transcriptome alteration. Epigenetic processes regulate DNA replication and repair, RNA transcription, and chromatin conformation, which in turn further dictate transcriptional regulation and protein translation. Transcriptional and post-transcriptional epigenetic regulation is mediated by enzymes and chromatin-modifying complexes that control DNA methylation, histone modifications, and RNA editing. While the alteration of DNA methylation and histone modification has recently been reported in ALS and FTD, the assessment of epigenetic involvement in both diseases is still at an early stage, and the involvement of multiple epigenetic players still needs to be evaluated. As the epigenome serves as a way to alter genetic information not only during aging, but also following environmental signals, epigenetic mechanisms might play a central role in initiating ALS and FTD, especially for sporadic cases. Here, we provide a review of what is currently known about altered epigenetic processes in both ALS and FTD and discuss potential therapeutic strategies targeting epigenetic mechanisms. As approximately 85 % of ALS and FTD cases are still genetically unexplained, epigenetic therapeutics explored for other diseases might represent a profitable direction for the field.
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Metadata
Title
ALS and FTD: an epigenetic perspective
Authors
Veronique V. Belzil
Rebecca B. Katzman
Leonard Petrucelli
Publication date
01-10-2016
Publisher
Springer Berlin Heidelberg
Published in
Acta Neuropathologica / Issue 4/2016
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-016-1587-4

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