The O-GlcNAc cycling in neurodevelopment and associated diseases

Proper neuronal development is essential to growth and adult brain function. Alterations at any step of this highly organized sequence of events, due to genetic mutations or environmental factors, triggers brain malformations, which are leading causes of diseases including epilepsy, intellectual disabilities, and many others. The role of glycosylation in neuronal development has been emphasized for many years, notably in studying human congenital disorders of glycosylation (CDGs). These diseases highlight that genetic defects in glycosylation pathways are almost always associated with severe neurological abnormalities, suggesting that glycosylation plays an essential role in early brain development. Congenital disorders of O-GlcNAcylation are no exception, and all mutations of the O-GlcNAc transferase (OGT) are associated with X-linked intellectual disabilities (XLID). In addition, mouse models and in vitro mechanistic studies have reinforced the essential role of O-GlcNAcylation in neuronal development and signaling. In this review, we give an overview of the role of O-GlcNAcylation in this critical physiological process and emphasize the consequences of its dysregulation.

Automated summary

Proper neuronal development is crucial for growth and adult brain function, with genetic mutations or environmental factors potentially leading to brain malformations and diseases like epilepsy and intellectual disabilities. The role of glycosylation in neuronal development is significant, as genetic defects in this pathway are often associated with severe neurological abnormalities. O-GlcNAcylation plays an essential role in neuronal development and signaling, with mutations in O-GlcNAc transferase (OGT) linked to X-linked intellectual disabilities (XLID).