Aggrecan core protein (ACAN) (ACAN)

Proteoglycan core proteins, primarily Aggrecan, are the major non-collagenous components of the intervertebral disc (IVD) extracellular matrix, particularly within the nucleus pulposus (UniProt P16112). These proteins are characterized by a central protein core to which numerous glycosaminoglycan (GAG) chains, such as chondroitin sulfate and keratan sulfate, are covalently attached (Roughley, 2006). The high fixed charge density of these GAGs creates an osmotic gradient that draws water into the disc, providing the hydrostatic pressure necessary to resist compressive loads and maintain disc height (Sivan et al., 2006). In the context of intervertebral disc degeneration (IDD), the proteolytic cleavage of these core proteins by enzymes like ADAMTS-4 and ADAMTS-5 leads to a loss of GAGs, dehydration, and subsequent mechanical failure of the disc (Gendron et al., 2007). Historically, these proteins were targeted for degradation by Chymopapain in chemonucleolysis to treat disc herniation by reducing intradiscal pressure (DrugBank DB00574). Modern therapeutic strategies focus on regenerating these proteins through the delivery of growth factors, mesenchymal stem cells, or peptides like Link N to restore the disc's structural and functional integrity (Mwale et al., 2011).

Other names

Proteoglycan core proteinsAggrecanACANChondroitin sulfate proteoglycan 1CSPG1Large aggregating proteoglycanVersicanDecorinBiglycan

Proteolytic degradation of the core protein to reduce intradiscal pressure (chemonucleolysis) or stimulation of core protein synthesis to restore disc hydration and mechanical function (anabolic therapy).