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Myotonic Dystrophy: an RNA Toxic Gain of Function Tauopathy?

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Tau Biology

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1184))

Abstract

Myotonic dystrophies (DM) are rare inherited neuromuscular disorders linked to microsatellite unstable expansions in non-coding regions of ubiquitously expressed genes. The DMPK and ZNF9/CNBP genes which mutations are responsible for DM1 and DM2 respectively. DM are multisystemic disorders with brain affection and cognitive deficits. Brain lesions consisting of neurofibrillary tangles are often observed in DM1 and DM2 brain. Neurofibrillary tangles (NFT) made of aggregates of hyper and abnormally phosphorylated isoforms of Tau proteins are neuropathological lesions common to more than 20 neurological disorders globally referred to as Tauopathies. Although NFT are observed in DM1 and DM2 brain, the question of whether DM1 and DM2 are Tauopathies remains a matter of debate. In the present review, several pathophysiological processes including, missplicing, nucleocytoplasmic transport disruption, RAN translation which are common mechanisms implicated in neurodegenerative diseases will be described. Together, these processes including the missplicing of Tau are providing evidence that DM1 and DM2 are not solely muscular diseases but that their brain affection component share many similarities with Tauopathies and other neurodegenerative diseases. Understanding DM1 and DM2 pathophysiology is therefore valuable to more globally understand other neurodegenerative diseases such as Tauopathies but also frontotemporal lobar neurodegeneration and amyotrophic lateral sclerosis.

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Authors and Affiliations

  1. University of Lille, INSERM, CHU-Lille, UMR-S 1172 – Alzheimer & Tauopathies, LabEx DISTALZ, Lille, France

    Francisco Fernandez-Gomez, Claire-Marie Dhaenens, Marie-Laure Caillet-Boudin, Susanna Schraen-Maschke, David Blum, Bernard Sablonnière, Valérie Buée-Scherrer, Luc Buee & Nicolas Sergeant

  2. Area of Pharmaceutical Technology. Group of Cellular and Molecular Pharmacology, Department of Pharmacology, University of Murcia. Murcia Research Institute of Health Sciences (IMIB-Arrixaca), Murcia, Spain

    Francisco Fernandez-Gomez

  3. Department of Neurology, Albert Sherman Center, University of Massachusetts Medical School, Worcester, MA, USA

    Helene Tran

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  1. Francisco Fernandez-Gomez
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  10. Nicolas Sergeant
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Correspondence to Nicolas Sergeant .

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  1. Department of Life Sciences, Gakushuin University, Tokyo, Japan

    Akihiko Takashima

  2. Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA

    Benjamin Wolozin

  3. University of Lille, INSERM, CHU-Lille, Alzheimer & Tauopathies, LabEx DISTALZ, Lille, France

    Luc Buee

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Fernandez-Gomez, F. et al. (2019). Myotonic Dystrophy: an RNA Toxic Gain of Function Tauopathy?. In: Takashima, A., Wolozin, B., Buee, L. (eds) Tau Biology. Advances in Experimental Medicine and Biology, vol 1184. Springer, Singapore. https://doi.org/10.1007/978-981-32-9358-8_17

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