Sphingolipids in Gaucher disease: a systematic review.

Gaucher disease (GD) is a rare lysosomal disorder of sphingolipid catabolism, characterised by a block in the degradation of glucosylceramide (GlcCer) to ceramide. The resulting effect is lysosomal accumulation of GlcCer and its deacylated derivative, glucosylsphingosine. Secondary alterations in the sphingolipid metabolic pathway have been reported, including elevated concentrations of ceramide, lactosylceramide (dihexosylceramide (DHC)), and gangliosides, however, there are notable inconsistencies across different cell and tissue types and their relevance to GD pathology is not well-understood. Sphingolipids are crucial for the regulation of intra- and extracellular functions and different cell types have different requirements. For example, neurons have a high demand for complex sphingolipids due to their extensive membrane remodelling networks necessary for their communication role. We therefore performed literature searches of PubMed, Scopus, and Web of Science databases to coalesce reports of sphingolipids in different animal and cell models of GD, as well as human cells and tissues from 1965 to 2024, totalling 54 studies. We found that DHC, trihexosylceramide, and simple gangliosides, G