Keratan Sulfate Restricts Neural Plasticity after Spinal Cord Injury

Abstract

Chondroitin sulfate (CS) proteoglycans are strong inhibitors of structural rearrangement after injuries of the adult CNS. In addition to CS chains, keratan sulfate (KS) chains are also covalently attached to some proteoglycans. CS and KS sometimes share the same core protein, but exist as independent sugar chains. However, the biological significance of KS remains elusive. Here, we addressed the question of whether KS is involved in plasticity after spinal cord injury. Keratanase II (K-II) specifically degraded KS, i.e., not CS, in vivo. This enzyme digestion promoted the recovery of motor and sensory function after spinal cord injury in rats. Consistent with this, axonal regeneration/ sprouting was enhanced in K-II-treated rats. K-II and the CS-degrading enzyme chondroitinase ABC exerted comparable effects in vivo and in vitro. However, these two enzymes worked neither additively nor synergistically. These data and further in vitro studies involving artificial proteoglycans (KS/CS-albumin) and heat-denatured or reduced/alkylated proteoglycans suggested that all three components of the proteoglycan moiety, i.e., the core protein, CS chains, and KS chains, were required for the inhibitory activity of proteoglycans. We conclude that KS is essential for, and has an impact comparable to that of CS on, postinjury plasticity. Our study also established that KS and CS are independent requirements for the proteoglycan-mediated inhibition of axonal regeneration/sprouting.

Di-sulfated Keratan Sulfate as a Novel Biomarker for Mucopolysaccharidosis II, IVA, and IVB

“…KS is involved in specific biological functions including tissue hydration, cellular recognition of protein ligands, axonal guidance, cell motility, and embryo implantation (Chakravarti et al 1998;Weyers et al 2013;Imagama et al 2011;Funderburgh et al 1997;Graham et al 1994). KS has been implicated in physiological and pathological status: (1) cushion in joints, (2) glial scar formation in spinal cord injury, (3) transparency in the cornea, and (4) skeletal dysplasia in patients with MPS IV.…”

Effects of Ashwagandha (Roots of <i>Withania somnifera</i>) on Neurodegenerative Diseases

“…In neurodegenerative diseases, neuronal networks are believed not spontaneously regenerated by distinct causes; for example, amyloid β (Aβ) induces axonal atrophy in Alzheimer's disease, and inhibitory proteoglycans inhibit regeneration of axons in spinal cord injury. [1][2][3][4][5][6][7][8][9][10] Although several drugs are clinically used for the treatment of neurodegenerative diseases, most of these drugs are for symptomatic treatment; drugs for fundamental cure of neurodegenerative diseases are not clinically available and greatly needed.…”

Current therapy of spinal cord injury

“…Then, C-ABC was used for preclinical trial. It was reported that sensory neuron and motor neuron are re-connected when C-ABC was administrated in the subarachnoid of SCI mice [20]. Recently not only CSPG but also KSPG regulation have been attempted.…”