Abstract
Proteoglycans consist of proteins linked to sulfated glycosaminoglycan chains. They constitute a family of macromolecules mainly involved in the architecture of organs and tissues as major components of extracellular matrices. Some proteoglycans also act as signaling molecules involved in inflammatory response as well as cell proliferation, adhesion, and differentiation. Inborn errors of proteoglycan metabolism are a group of orphan diseases with severe and irreversible skeletal abnormalities associated with multiorgan impairments. Identifying the gene variants that cause these pathologies proves to be difficult because of unspecific clinical symptoms, hardly accessible functional laboratory tests, and a lack of convenient blood biomarkers. In this review, we summarize the molecular pathways of proteoglycan biosynthesis, the associated inherited syndromes, and the related biochemical screening techniques, and we focus especially on a circulating proteoglycan called bikunin and on its potential as a new biomarker of these diseases.
Highlights
Proteoglycans (PGs) consist of core proteins linked to sulfated glycosaminoglycan (GAG) chains
They consist of three isoforms, i.e., one light form (35 to 45 kDa) corresponding to the core Bkn linked to a short chondroitin sulfate (CS) chain (Bkn–CS), and two heavy forms named Pro-αtrypsin inhibitor (PαI) (125 kDa) and Inter-α-trypsin inhibitor (ITI) (225 kDa)
The biosynthesis of PGs constitutes an intricate network of diverse metabolic pathways whose study proves to be a daunting task
Summary
Proteoglycans (PGs) consist of core proteins linked to sulfated glycosaminoglycan (GAG) chains. They constitute a family of around fifty macromolecules involved in a wide variety of pathophysiological processes in humans [1]. The causative variants occur in genes that encode enzymes responsible for the elongation and modifications of the GAG chains. Mucopolysaccharidoses (MPS), a group of diseases resulting from defective GAG catabolism, have very similar clinical presentations to PG-IMD They are caused by pathogenic variants in genes encoding lysosomal GAG-degrading enzymes leading to deleterious GAG accumulation in tissues [9]. Except for KSPGs, the GAG chains are linked to serine (Ser) residues of the core proteins through a common tetrasaccharide linker motif [(glucuronic acid–galactose–galactose–xylose) abbreviated as (GlcA–Gal–Gal–Xyl)].
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