Work

Protein glycosylation and synaptic transmission: brain glycogen keeps them separated

Year: 2025

Type: article

Abstract: Brain glycogen has long been regarded uniquely as a source of energetic support in situations of emergency or heightened activity. Recently, brain glycogen was found to contain a significant amount of glucosamine, which is used to sustain protein glycosylation. In this update, we highlight that glucosamine synthesis through the hexosamine pathway would subtract glutamine, which is indispensable for glutamate and GABA recycling. Brain glycogen seems then to serve an additional role. By providing glucosamine and, through it, inhibiting the hexosamine pathway, glycogen avoids glutamine depletion. In neurological glycogen storage diseases, the short-circuit between the hexosamine pathway and neurotransmitter recycling can cause epileptic seizures, which are the most common acute manifestation in these pathologies. We finally discuss the metabolic and symptomatic superposition of glycogen storage diseases with congenital disorders of glycosylation, concluding that treatments ameliorating the clinical symptoms in some of the discussed pathologies could also be beneficial in others.

Source: Brain

DOI: 10.1093/brain/awaf396

Authors: Gabriele Trentini, Giulia Cazzanelli, Graziano Lolli

Institution: University of Trento

Language: English

Topic: Glycogen Storage Diseases and Myoclonus

Subfield: Rheumatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,570