Myotonic dystrophy 1 in the nervous system: From the clinic to molecular mechanisms

Mario Bermúdez De León, Bulmaro Cisneros Vega

Research output: Contribution to journalShort survey

27 Citations (Scopus)

Abstract

Myotonic dystrophy type 1 (DM1) is a dominant neuromuscular disorder caused by the expansion of trinucleotide CTG repeats in the 3′-untranslated region (3′-UTR) of the DMPK gene. Prominent features of classical DM1 are muscle wasting and myotonia, whereas mental retardation is distinctive for congenital DM1. The main nervous system symptoms of DM1 are cognitive impairment, neuroendocrine dysfunction, and personality and behavior abnormalities. It is thought that expansion of CTG repeats causes DM1 pathology through different molecular mechanisms; however, a growing body of evidence indicates that an RNA gain-of-function mechanism plays a major role in the disease development. At the skeletal muscle level, three main molecular events can be distinguished in this model: 1) formation of nuclear foci that are composed at least of mutant DMPK mRNA and recruited RNA-binding proteins, such as splicing regulators and transcription factors; 2) disturbance of alternative splicing of specific genes; and 3) impairment of cell differentiation. Contrasting with the substantial advances in understanding DM1 muscle pathology, the molecular basis of DM1 in the nervous system has just started to be revealed. This review focuses in the DM1 nervous system pathology and provides an overview of the genetic and molecular studies analyzing the effects of the DMPK gene CUG expanded repeats on cell function in neuronal systems. A comparison between the molecular mechanisms of DM1 in the skeletal muscle and those identified in DM1 nervous system models is provided. Finally, future directions in the study of DM1 in the nervous system are discussed. © 2007 Wiley-Liss, Inc.
Original languageEnglish
Pages (from-to)18-26
Number of pages9
JournalJournal of Neuroscience Research
DOIs
Publication statusPublished - 1 Jan 2008
Externally publishedYes

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Myotonic Dystrophy
Nervous System
Skeletal Muscle
Trinucleotide Repeat Expansion
Myotonia
Pathology
Genes
Muscles
RNA-Binding Proteins
Molecular Pathology
Alternative Splicing
3' Untranslated Regions
Intellectual Disability
Personality
Molecular Biology
Cell Differentiation
Transcription Factors
RNA
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Cite this

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title = "Myotonic dystrophy 1 in the nervous system: From the clinic to molecular mechanisms",
abstract = "Myotonic dystrophy type 1 (DM1) is a dominant neuromuscular disorder caused by the expansion of trinucleotide CTG repeats in the 3′-untranslated region (3′-UTR) of the DMPK gene. Prominent features of classical DM1 are muscle wasting and myotonia, whereas mental retardation is distinctive for congenital DM1. The main nervous system symptoms of DM1 are cognitive impairment, neuroendocrine dysfunction, and personality and behavior abnormalities. It is thought that expansion of CTG repeats causes DM1 pathology through different molecular mechanisms; however, a growing body of evidence indicates that an RNA gain-of-function mechanism plays a major role in the disease development. At the skeletal muscle level, three main molecular events can be distinguished in this model: 1) formation of nuclear foci that are composed at least of mutant DMPK mRNA and recruited RNA-binding proteins, such as splicing regulators and transcription factors; 2) disturbance of alternative splicing of specific genes; and 3) impairment of cell differentiation. Contrasting with the substantial advances in understanding DM1 muscle pathology, the molecular basis of DM1 in the nervous system has just started to be revealed. This review focuses in the DM1 nervous system pathology and provides an overview of the genetic and molecular studies analyzing the effects of the DMPK gene CUG expanded repeats on cell function in neuronal systems. A comparison between the molecular mechanisms of DM1 in the skeletal muscle and those identified in DM1 nervous system models is provided. Finally, future directions in the study of DM1 in the nervous system are discussed. {\circledC} 2007 Wiley-Liss, Inc.",
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Myotonic dystrophy 1 in the nervous system: From the clinic to molecular mechanisms. / De León, Mario Bermúdez; Cisneros Vega, Bulmaro.

In: Journal of Neuroscience Research, 01.01.2008, p. 18-26.

Research output: Contribution to journalShort survey

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