Abstract
α-Dystroglycanopathy, an autosomal recessive disease, is associated with the development of a variety of diseases, including muscular dystrophy. In humans, α-dystroglycanopathy includes various types of congenital muscular dystrophy such as Fukuyama type congenital muscular dystrophy (FCMD), muscle eye brain disease (MEB), and the Walker Warburg syndrome (WWS), and types of limb girdle muscular dystrophy 2I (LGMD2I). α-Dystroglycanopathy share a common etiology, since it is invariably caused by gene mutations that are associated with the O-mannose glycosylation pathway of α-dystroglycan (α-DG). α-DG is a central member of the dystrophin glycoprotein complex (DGC) family in peripheral membranes, and the proper glycosylation of α-DG is essential for it to bind to extracellular matrix proteins, such as laminin, to cell components. The disruption of this ligand-binding is thought to result in damage to cell membrane integration, leading to the development of muscular dystrophy. Clinical manifestations of α-dystroglycanopathy frequently include mild to severe alterations in the central nervous system and optical manifestations in addition to muscular dystrophy. Eighteen causative genes for α-dystroglycanopathy have been identified to date, and it is likely that more will be reported in the near future. These findings have stimulated extensive and energetic investigations in this research field, and novel glycosylation pathways have been implicated in the process. At the same time, the use of gene therapy, antisense therapy, and enzymatic supplementation have been evaluated as therapeutic possibilities for some types of α-dystroglycanopathy. Here we review the molecular and clinical findings associated with α-dystroglycanopathy and the development of therapeutic approaches, by comparing the approaches with the development of Duchenne muscular dystrophy.
| Original language | English |
|---|---|
| Pages (from-to) | 115-124 |
| Number of pages | 10 |
| Journal | Molecular Aspects of Medicine |
| Volume | 51 |
| DOIs | |
| Publication status | Published - 01-10-2016 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry
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Mechanistic aspects of the formation of α-dystroglycan and therapeutic research for the treatment of α-dystroglycanopathy : A review. / Ikeda, Mariko; Morioka, Ichiro; Iijima, Kazumoto; Toda, Tatsushi.
In: Molecular Aspects of Medicine, Vol. 51, 01.10.2016, p. 115-124.Research output: Contribution to journal › Review article
TY - JOUR
T1 - Mechanistic aspects of the formation of α-dystroglycan and therapeutic research for the treatment of α-dystroglycanopathy
T2 - A review
AU - Ikeda, Mariko
AU - Morioka, Ichiro
AU - Iijima, Kazumoto
AU - Toda, Tatsushi
PY - 2016/10/1
Y1 - 2016/10/1
N2 - α-Dystroglycanopathy, an autosomal recessive disease, is associated with the development of a variety of diseases, including muscular dystrophy. In humans, α-dystroglycanopathy includes various types of congenital muscular dystrophy such as Fukuyama type congenital muscular dystrophy (FCMD), muscle eye brain disease (MEB), and the Walker Warburg syndrome (WWS), and types of limb girdle muscular dystrophy 2I (LGMD2I). α-Dystroglycanopathy share a common etiology, since it is invariably caused by gene mutations that are associated with the O-mannose glycosylation pathway of α-dystroglycan (α-DG). α-DG is a central member of the dystrophin glycoprotein complex (DGC) family in peripheral membranes, and the proper glycosylation of α-DG is essential for it to bind to extracellular matrix proteins, such as laminin, to cell components. The disruption of this ligand-binding is thought to result in damage to cell membrane integration, leading to the development of muscular dystrophy. Clinical manifestations of α-dystroglycanopathy frequently include mild to severe alterations in the central nervous system and optical manifestations in addition to muscular dystrophy. Eighteen causative genes for α-dystroglycanopathy have been identified to date, and it is likely that more will be reported in the near future. These findings have stimulated extensive and energetic investigations in this research field, and novel glycosylation pathways have been implicated in the process. At the same time, the use of gene therapy, antisense therapy, and enzymatic supplementation have been evaluated as therapeutic possibilities for some types of α-dystroglycanopathy. Here we review the molecular and clinical findings associated with α-dystroglycanopathy and the development of therapeutic approaches, by comparing the approaches with the development of Duchenne muscular dystrophy.
AB - α-Dystroglycanopathy, an autosomal recessive disease, is associated with the development of a variety of diseases, including muscular dystrophy. In humans, α-dystroglycanopathy includes various types of congenital muscular dystrophy such as Fukuyama type congenital muscular dystrophy (FCMD), muscle eye brain disease (MEB), and the Walker Warburg syndrome (WWS), and types of limb girdle muscular dystrophy 2I (LGMD2I). α-Dystroglycanopathy share a common etiology, since it is invariably caused by gene mutations that are associated with the O-mannose glycosylation pathway of α-dystroglycan (α-DG). α-DG is a central member of the dystrophin glycoprotein complex (DGC) family in peripheral membranes, and the proper glycosylation of α-DG is essential for it to bind to extracellular matrix proteins, such as laminin, to cell components. The disruption of this ligand-binding is thought to result in damage to cell membrane integration, leading to the development of muscular dystrophy. Clinical manifestations of α-dystroglycanopathy frequently include mild to severe alterations in the central nervous system and optical manifestations in addition to muscular dystrophy. Eighteen causative genes for α-dystroglycanopathy have been identified to date, and it is likely that more will be reported in the near future. These findings have stimulated extensive and energetic investigations in this research field, and novel glycosylation pathways have been implicated in the process. At the same time, the use of gene therapy, antisense therapy, and enzymatic supplementation have been evaluated as therapeutic possibilities for some types of α-dystroglycanopathy. Here we review the molecular and clinical findings associated with α-dystroglycanopathy and the development of therapeutic approaches, by comparing the approaches with the development of Duchenne muscular dystrophy.
UR - http://www.scopus.com/inward/record.url?scp=84979672144&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979672144&partnerID=8YFLogxK
U2 - 10.1016/j.mam.2016.07.003
DO - 10.1016/j.mam.2016.07.003
M3 - Review article
C2 - 27421908
AN - SCOPUS:84979672144
VL - 51
SP - 115
EP - 124
JO - Molecular Aspects of Medicine
JF - Molecular Aspects of Medicine
SN - 0098-2997
ER -