Myo-Glyco disease Biology: Genetic Myopathies Caused by Abnormal Glycan Synthesis and Degradation

Glycosylation is a major form of post-translational modification and plays various important roles in organisms by modifying proteins or lipids, which generates functional variability and can increase their stability. Because of the physiological importance of glycosylation, defects in genes encoding proteins involved in glycosylation or glycan degradation are sometimes associated with human diseases. A number of genetic neuromuscular diseases are caused by abnormal glycan modification or degeneration. Heterogeneous and complex modification machinery, and difficulties in structural and functional analysis of glycans have impeded the understanding of how glycosylation contributes to pathology. However, recent rapid advances in glycan and genetic analyses, as well as accumulating genetic and clinical information have greatly contributed to identifying glycan structures and modification enzymes, which has led to breakthroughs in the understanding of the molecular pathogenesis of various diseases and the possible development of therapeutic strategies. For example, studies on the relationship between glycosylation and muscular dystrophy in the last two decades have significantly impacted the fields of glycobiology and neuromyology. In this review, the basis of glycan structure and biosynthesis will be briefly explained, and then molecular pathogenesis and therapeutic concepts related to neuromuscular diseases will be introduced from the point of view of the life cycle of a glycan molecule.