Modulation of glycosylation in the brain: A single-cell exploration of glycosidases using the Allen Brain Cell Atlas

The mammalian brain is enveloped in a dense, charge-rich glycocalyx that orchestrates cell signalling, migration, and synaptic stability. Transcriptomic explorations of this molecular interface have previously focussed on the complex enzymatic machinery of glycan synthesis. However, relying on glycosyltransferase expression only, ignores the existence of rate-limiting factors. In this Perspective, we use the high-resolution single-cell data in the Allen Brain Cell (ABC) Atlas to shift the glycoanalytical lens from synthesis to degradation. By mapping the spatial expression of feature-specific glycosidases, we reveal that glycan remodelling is not a generic housekeeping function, but is a highly segregated strategy defined by discrete abundances in specific cellular populations and brain regions. Here we present some distinct "eraser" glycosidase profiles to raise critical, unexplored questions regarding their biological relevance. We suggest that the selective deployment of these enzymes may represent a fundamental, yet overlooked, mechanism for fine-tuning the brain's local electrostatic and functional environment.