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α-Dystroglycanopathy

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Translational Research in Muscular Dystrophy

Abstract

α-Dystroglycanopathy encompasses a group of congenital and limb-girdle-type muscular dystrophies that are caused by abnormal glycosylation of α-dystroglycan. α-Dystroglycanopathy is often associated with brain abnormalities including type II lissencephaly and mental retardation. Currently, around 15 genes have been identified in which mutations cause abnormal glycosylation of α-dystroglycan resulting in disease. Dystroglycan is a highly glycosylated peripheral membrane protein that functions as a cell-surface receptor for proteins in the extracellular matrices and synapses. Unique O-mannosyl glycosylation is necessary for the ligand-binding activities of dystroglycan, and some of α-dystroglycanopathy gene products are involved in the process of α-dystroglycan glycosylation. Studies using animal and cell models for α-dystroglycanopathy have contributed to understanding the pathogenesis of this disease and to establishing therapeutic strategies. In this chapter, we review the structure, modification pathways, and physiological roles of dystroglycan glycosylation, as well as their involvement in human diseases, disease pathogenesis, and therapeutic strategies.

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Authors and Affiliations

  1. Division of Molecular Brain Science, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan

    Motoi Kanagawa & Tatsushi Toda

  2. Division of Neurology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo, 650-0017, Japan

    Tatsushi Toda

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  1. Motoi Kanagawa
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  2. Tatsushi Toda
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Correspondence to Motoi Kanagawa .

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  1. National Institute of Neuroscience, Kodaira, Tokyo, Tokyo, Japan

    Shin'ichi Takeda

  2. National Institute of Neuroscience, Kodaira, Tokyo, Tokyo, Japan

    Yuko Miyagoe-Suzuki

  3. National Institute of Neuroscience, Kodaira, Tokyo, Tokyo, Japan

    Madoka Mori-Yoshimura

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Kanagawa, M., Toda, T. (2016). α-Dystroglycanopathy. In: Takeda, S., Miyagoe-Suzuki, Y., Mori-Yoshimura, M. (eds) Translational Research in Muscular Dystrophy. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55678-7_2

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