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Molecular Neurobiology

, Volume 56, Issue 4, pp 2579–2589 | Cite as

R-Loops in Motor Neuron Diseases

  • Martina G. L. Perego
  • Michela Taiana
  • Nereo Bresolin
  • Giacomo P. Comi
  • Stefania CortiEmail author
Article

Abstract

R loops are transient three-stranded nucleic acid structures that form physiologically during transcription when a nascent RNA transcript hybridizes with the DNA template strand, leaving a single strand of displaced nontemplate DNA. However, aberrant persistence of R-loops can cause DNA damage by inducing genomic instability. Indeed, evidence has emerged that R-loops might represent a key element in the pathogenesis of human diseases, including cancer, neurodegeneration, and motor neuron disorders. Mutations in genes directly involved in R-loop biology, such as SETX (senataxin), or unstable DNA expansion eliciting R-loop generation, such as C9ORF72 HRE, can cause DNA damage and ultimately result in motor neuron cell death. In this review, we discuss current advancements in this field with a specific focus on motor neuron diseases associated with deregulation of R-loop structures. These mechanisms can represent novel therapeutic targets for these devastating, incurable diseases.

Keywords

R-loops DNA damage Motor neuron disease Amyotrophic lateral sclerosis Spinal muscular atrophy 

Notes

Acknowledgments

Joint Programme Neurodegenerative Disease (JPND) Research grant DAMNDPATHS (2014) and ARISLA grant smallRNALS (2014) to SC and the Italian Ministry of Health RF- 2013-023555764 and Regione Lombardia TRANS-ALS to GPC are gratefully acknowledged. The authors wish to thank the Associazione Centro Dino Ferrari for its support.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), Neurology Unit, IRCCS Foundation Ca’ Granda Ospedale Maggiore PoliclinicoUniversity of MilanMilanItaly

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