Increased levels of expression of dystroglycan may protect the heart

Dystroglycan is a major adhesion complex composed of two subunits, α and β, that undergoes extensive post-translational modifications. In particular, its α subunit is heavily decorated with sugars, influencing its basement membrane binding properties. An altered glycosylation of α-dystroglycan is at the molecular basis of muscular dystrophies defined as secondary dystroglycanopathies, that depend on malfunctioning of the enzymes in the glycosylation pathway. An increased level of transcription of the dystroglycan gene may be crucial for obtaining sufficient amounts of dystroglycan precursor substrate required for the production of the heavily glycosylated and fully functional α-dystroglycan molecule. Even slight differences in these transcriptional levels may exert a protective or pathogenetic effect, as discussed for the unique case of primary dystroglycanopathy so far identified (T192M), where the heart tissues are not affected by the pathology. Moreover, the N-terminal fragment of α-dystroglycan is also proposed to have a regulatory role in the glycosylation/maturation process.