The Therapeutic Future for Congenital Disorders of Glycosylation.

The past decade, novel treatment options for congenital disorders of glycosylation (CDG) have advanced rapidly. Innovative therapies, targeting both the root cause, the affected metabolic pathways, and resulting manifestations, have transitioned from the research stage to practical applications. However, with novel therapeutic abilities, novel challenges await, specifically when it concerns the large number of clinical trials that need to be performed in order to treat all 190 genetic defects that cause CDG known to date.

N-glycoproteomic and proteomic alterations in SRD5A3-deficient fibroblasts.

SRD5A3-CDG is a congenital disorder of glycosylation (CDG) resulting from pathogenic variants in SRD5A3 and follows an autosomal recessive inheritance pattern. The enzyme encoded by SRD5A3, polyprenal reductase, plays a crucial role in synthesizing lipid precursors essential for N-linked glycosylation. Despite insights from functional studies into its enzymatic function, there remains a gap in understanding global changes in patient cells.

Evolutionary rescue of phosphomannomutase deficiency in yeast models of human disease.

The most common cause of human congenital disorders of glycosylation (CDG) are mutations in the phosphomannomutase gene which affect protein -linked glycosylation. The yeast gene encodes a homolog of human . We evolved 384 populations of yeast harboring one of two human-disease-associated alleles, V238M and -F126L, or wild-type .

Glial control of sphingolipid levels sculpts diurnal remodeling in a circadian circuit.

Structural plasticity in the brain often necessitates dramatic remodeling of neuronal processes, with attendant reorganization of the cytoskeleton and membranes. Although cytoskeletal restructuring has been studied extensively, how lipids might orchestrate structural plasticity remains unclear. We show that specific glial cells in Drosophila produce glucocerebrosidase (GBA) to locally catabolize sphingolipids.