Molecular mechanisms of muscle atrophy in myotonic dystrophies.
Int J Biochem Cell Biol
; 45(10): 2280-7, 2013 Oct.
Article
en En
| MEDLINE
| ID: mdl-23796888
ABSTRACT
Myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) are multisystemic diseases that primarily affect skeletal muscle, causing myotonia, muscle atrophy, and muscle weakness. DM1 and DM2 pathologies are caused by expansion of CTG and CCTG repeats in non-coding regions of the genes encoding myotonic dystrophy protein kinase (DMPK) and zinc finger protein 9 (ZNF9) respectively. These expansions cause DM pathologies through accumulation of mutant RNAs that alter RNA metabolism in patients' tissues by targeting RNA-binding proteins such as CUG-binding protein 1 (CUGBP1) and Muscle blind-like protein 1 (MBNL1). Despite overwhelming evidence showing the critical role of RNA-binding proteins in DM1 and DM2 pathologies, the downstream pathways by which these RNA-binding proteins cause muscle wasting and muscle weakness are not well understood. This review discusses the molecular pathways by which DM1 and DM2 mutations might cause muscle atrophy and describes progress toward the development of therapeutic interventions for muscle wasting and weakness in DM1 and DM2. This article is part of a Directed Issue entitled Molecular basis of muscle wasting.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Atrofia Muscular
/
Músculo Esquelético
/
Trastornos Miotónicos
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Distrofia Miotónica
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Biochem Cell Biol
Asunto de la revista:
BIOQUIMICA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos