TY - JOUR
T1 - Mechanistic aspects of the formation of α-dystroglycan and therapeutic research for the treatment of α-dystroglycanopathy
T2 - A review
AU - Taniguchi-Ikeda, Mariko
AU - Morioka, Ichiro
AU - Iijima, Kazumoto
AU - Toda, Tatsushi
N1 - Funding Information:
We thank Dr. Milton S Feather for precise editing of this manuscript. We thank Tatsuro Ikeda for drawing the figures. This work is supported by the National Center of Neurology and Psychiatry (NCNP; Intramural Research Grant 26-8 to T.T.), Japan Agency for Medical Research and Development (AMED; 15dk0310041h0002 to T.T. and M.T.I.), Project Promoting Clinical Trials for Development of New Drugs and Medical Devices from Japan Agency for Medical Research and development (AMED; 15lk0201027h0002 to T.T. and M.T.I.), Grant-in-Aid for Scientific Research , (KAKENHI; 15K09621 to M.T.I), Hoansha Foundation (to M.T.I). K.I. has received grants from Novartis Pharma K.K., Japan Blood Product Organization, Pfizer Japan, Inc., Kyowa Hakko Kirin Co., Ltd., AbbVie LLC, JCR Pharmaceuticals Co., Ltd., Daiichi Sankyo, Co., Ltd., Genzyme Japan K.K., Teijin Pharma Ltd., Miyarisan Pharmaceutical Co., Ltd., CSL Behring, Novo Nordisk Pharma Ltd., AIR WATER MEDICAL Inc., and Astellas Pharma Inc.; lecture fees from Pfizer Japan, Inc., Asahi Kasei Pharma Corp., Kowa Pharmaceutical Co., Ltd., MSD, ALEXION Pharmaceuticals, AstraZeneca K.K., Meiji Seika Pharma Co., Ltd., Novartis Pharma K.K., Zenyaku Kogyo Co., Ltd., Daiichi Sankyo, Co., Ltd., Springer Japan, Medical Review Co. Ltd., Chugai Pharmaceutical Co., Ltd., Boehringer Ingelheim, and Nikkei Radio Broadcasting Corporation; manuscript fees from Chugai Pharmaceutical Co., Ltd.; and consulting fees from Zenyaku Kogyo Co., Ltd., Astellas Pharma Inc., Ono Pharmaceutical Co., Ltd. and Takeda Pharmaceutical Company Limited.
Publisher Copyright:
© 2016 Elsevier Ltd
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.
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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 -