Ablation of keratan sulfate accelerates early phase pathogenesis of ALS.

Biopolymers consist of three major classes, i.e., polynucleotides (DNA, RNA), polypeptides (proteins) and polysaccharides (sugar chains).

Midkine overcomes neurite outgrowth inhibition of chondroitin sulfate proteoglycan without glial activation and promotes functional recovery after spinal cord injury.

Injuries in the mammalian central nervous system induce a variety of factors which promote or inhibit neuronal axon regeneration/sprouting. However, the inhibitory activities are much stronger, and indeed are the major obstacle to functional recovery. Chondroitin sulfate proteoglycans (CSPGs) are produced by activated glial cells, and are among the strongest inhibitors.

CD44 expression in astrocytes and microglia is associated with ALS progression in a mouse model.

Amyotrophic lateral sclerosis (ALS) is a motor neuron-specific neurodegenerative disease. An increasing body of evidence suggests that, in addition to cell autonomous regulation, i.e.

ADAMTS-13 is produced by glial cells and upregulated after spinal cord injury.

ADAMTS-13, a member of the family of disintegrins and metalloproteinases with thrombospondin motifs, is produced primarily in the liver, particularly by hepatic stellate cells. This metalloproteinase cleaves von Willebrand factor multimers and thereby regulates blood coagulation. Here, we investigated the expression of ADAMTS-13 in the central nervous system.

The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury.

Background: Chondroitin sulfate proteoglycans are major inhibitory molecules for neural plasticity under both physiological and pathological conditions. The chondroitin sulfate degrading enzyme chondroitinase ABC promotes functional recovery after spinal cord injury, and restores experience-dependent plasticity, such as ocular dominance plasticity and fear erasure plasticity, in adult rodents. These data suggest that the sugar chain in a proteoglycan moiety is essential for the inhibitory activity of proteoglycans.

Hyaluronan oligosaccharides promote functional recovery after spinal cord injury in rats.

Hyaluronan is a component of the extracellular matrix of the central nervous system, and forms perineuronal nets around neurons. It has been recently reported that the hyaluronan-degrading enzyme hyaluronidase promotes lateral mobility of AMPA-type glutamate receptors and enhances synaptic plasticity. However, the biological significance of hyaluronan-degrading products (oligosaccharides) has not been studied in depth.

Transforming growth factor-beta1 upregulates keratan sulfate and chondroitin sulfate biosynthesis in microglias after brain injury.

After injury to the adult central nervous system, levels of extracellular matrix molecules increase at the injury site and may inhibit the repair of injured axons. Among these molecules, the importance of proteoglycans, particularly their chondroitin sulfate chains, has been highlighted. We have recently reported that keratan sulfate-deficient mice show better axonal regeneration after injury.

Epigenetic disregulation induces cell growth retardation in primary cultured glial cells.

Some epigenetic mechanisms, including DNA methylation and histone deacetylation, act as transcriptional repression signals. In this study, we examined whether DNA methylation dependent transcriptional control regulates glial cell growth. Primary cultured mouse cortical glial cells were treated with the DNA methylation inhibitor 5-aza-deoxycytidine (5adC) or the histone deacetylase inhibitor sodium valproate (VPA), which inhibits DNA-methylation-dependent transcriptional repression.

Augmentation of polysialic acid by valproic acid in early postnatal mouse hippocampus and primary cultured hippocampal neurons.

We examined the effects of valproic acid (VPA) on hippocampal neurons. Prenatal VPA exposure significantly increased polysialic acid (PSA) expression in the early postnatal mouse hippocampus. Moreover, VPA treatment significantly enhanced PSA expression in primary cultured hippocampal neurons and stimulated neurite growth.

Endoplasmic reticulum stress upregulates the chondroitin sulfate level which thus prevents neurite extension in C6 glioma cells and primary cultured astrocytes.

Chondroitin sulfate (CS), which is known to be a neurite-preventing molecule, is a major component of the extracellular matrix (ECM) in the central nervous system (CNS). The CS expression is upregulated around damaged areas. Endoplasmic reticulum (ER) stress causes neuronal cell death in numerous neurodegenerative diseases.