Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.4 (chondroitinase)
 2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fibroblast growth factor (FGF)-2 regulates chondrocyte proliferation in the growth plate. Heparan sulfate (HS) proteoglycans bind FGF-2. Perlecan, a heparan sulfate proteoglycan (HSPG) in the developing growth plate, however, contains both HS and chondroitin sulfate (CS) chains. The binding of FGF-2 to perlecan isolated from the growth plate was evaluated using cationic filtration (CAF) and immunoprecipitation (IP) assays. FGF-2 bound to perlecan in both the CAF and IP assays primarily via the HS chains on perlecan. A maximum of 123 molecules of FGF-2 was calculated to bind per molecule of perlecan. When digested with chondroitinase ABC to remove its CS chains, perlecan augmented binding of FGF-2 to the FGFR-1 and FGFR-3 receptors and also increased FGF-2 stimulation of [(3)H]-thymidine incorporation in BaF3 cells expressing these FGF receptors. These data show that growth plate perlecan binds to FGF-2 by its HS chains but can only deliver FGF-2 to FGF receptors when its CS chains are removed.
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PMID:Heparan and chondroitin sulfate on growth plate perlecan mediate binding and delivery of FGF-2 to FGF receptors. 1716 45

The neural stem cell niche of the embryonic and adult forebrain is rich in chondroitin sulfate glycosaminoglycans (CS-GAGs) that represent complex linear carbohydrate structures on the cell surface of neural stem/progenitor cells or in their intimate environment. We reported earlier that the removal of CS-GAGs with the bacterial enzyme chondroitinase ABC (ChABC) reduced neural stem/progenitor cell proliferation and self-renewal, whereas this treatment favored astroglia formation at the expense of neurogenesis. Here, we studied the consequences of CS-deglycanation further and revealed that CS-GAGs are selectively required for neurosphere formation, proliferation, and self-renewal of embryonic cortical neural stem/progenitor cells in response to fibroblast growth factor (FGF)-2. Consistently, the FGF-2-dependent activation of the MAPKinase in neural stem/progenitor cells was diminished after ChABC treatment, but unaltered after epidermal growth factor (EGF) stimulation. Upon EGF treatment, fewer radial glia were brain lipid-binding protein (BLBP)-positive, whereas more were glutamate aspartate transporter (GLAST)-positive after CS-GAG removal. Only in this latter situation, GLAST-positive radial glia cells extended processes that supported neuronal migration from differentiating neurospheres. CS-deglycanation also selectively increased astrocyte numbers and their migration in response to EGF. Thus, our approach revealed that CS-GAGs are essential for FGF-2-mediated proliferation and maintenance of neuron-generating neural stem/progenitor cells. Simultaneously, CS-GAGs act as a brake on the EGF-dependent maturation, migration, and gliogenesis of neural stem/progenitor cells. We conclude that neural stem/progenitor cell subpopulations reside in neurospheres that are distinguishable by their responsiveness to FGF-2 and EGF which is differentially regulated by CS-carbohydrate structures.
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PMID:Chondroitin sulfates are required for fibroblast growth factor-2-dependent proliferation and maintenance in neural stem cells and for epidermal growth factor-dependent migration of their progeny. 2008 64

One of the big challenges in neuroscience that remains to be understood is why the central nervous system is not able to regenerate to the extent that the peripheral nervous system does. This is especially problematic after traumatic injuries, like spinal cord injury (SCI), since the lack of regeneration leads to lifelong deficits and paralysis. Treatment of SCI has improved during the last several decades due to standardized protocols for emergency medical response teams and improved medical, surgical, and rehabilitative treatments. However, SCI continues to result in profound impairments for the individual. There are many processes that lead to the pathophysiology of SCI, such as ischemia, vascular disruption, neuroinflammation, oxidative stress, excitotoxicity, demyelination, and cell death. Current treatments include surgical decompression, hemodynamic control, and methylprednisolone. However, these early treatments are associated with modest functional recovery. Some treatments currently being investigated for use in SCI target neuroprotective (riluzole, minocycline, G-CSF, FGF-2, and polyethylene glycol) or neuroregenerative (chondroitinase ABC, self-assembling peptides, and rho inhibition) strategies, while many cell therapies (embryonic stem cells, neural stem cells, induced pluripotent stem cells, mesenchymal stromal cells, Schwann cells, olfactory ensheathing cells, and macrophages) have also shown promise. However, since SCI has multiple factors that determine the progress of the injury, a combinatorial therapeutic approach will most likely be required for the most effective treatment of SCI.
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PMID:Translating mechanisms of neuroprotection, regeneration, and repair to treatment of spinal cord injury. 2589 Jan 31