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)

Many chondroitin sulfate proteoglycans (CSPGs) have been shown to influence CNS axon growth in vitro and in vivo. These interactions can be mediated through the core protein or through the chondroitin sulfate (CS) glycosaminoglycan (GAG) side chains. We have shown previously that degrading CS GAG side chains using chondroitinase ABC enhances dopaminergic nigrostriatal axon regeneration in vivo. We test the hypothesis that interfering with complete CSPGs also limit axon growth in vivo. Neurocan, versican, aggrecan, and brevican CSPGs may be anchored within extracellular matrix through binding to hyaluronan glycosaminoglycan. We examine whether degradation of hyaluronan using hyaluronidase might release these inhibitory CSPGs from the extracellular matrix and thereby enhance regeneration of cut nigrostriatal axons. Anesthetized adult rats were given knife cut lesions of the right hemisphere nigrostriatal tract and cannulae were secured transcranially thereby allowing repeated perilesional infusion of saline or saline containing hyaluronidase once daily for 10 days post-axotomy. Eleven days post-transection brains from animals under terminal anesthesia were recovered for histological evaluation. Effective delivery of substance was inferred from the observed reduction in perilesional immunoreactivity for neurocan and versican after treatment with hyaluronidase (relative to saline). Immunolabeling using antibodies against tyrosine hydroxylase was used to examine the response of cut dopaminergic nigral neurons. After transection and treatment with saline, dopaminergic nigral neurons sprouted in a region lacking astrocytes, neurocan and versican. Axons did not regenerate into the lesion surround that contained astrocytes and abundant neurocan and versican. After transection and treatment with hyaluronidase, there was a significant increase in the number of cut dopaminergic nigral axons growing up to 800 microm anterior to the site of transection. However, cut dopaminergic nigral axons still did not regenerate into the lesion surround that contained reduced (albeit residual) neurocan and versican immunoreactivity. Thus, partial degradation of hyaluronan and chondroitin sulfate and depletion of hyaluronan-binding CSPGs enhances local sprouting of cut CNS axons, but long-distance regeneration fails in regions containing residual hyaluronan-binding CSPGs. Hyaluronan, chondroitin sulfate and hyaluronan-binding CSPGs therefore likely contribute toward the failure of spontaneous axon regeneration in the injured adult mammalian brain and spinal cord.
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PMID:Limited growth of severed CNS axons after treatment of adult rat brain with hyaluronidase. 1247 11

Various pharmacologic vitreolysis agents, including hyaluronidase, urea, plasmin, dispase, tissue plasminogen activator and chondroitinase have been tested. Pharmacologic vitreolysis can avoid the complications of surgery such as cataract, endophthalmitis, retinal hemorrhage, tear or detachment, and anesthesia related complications. Hyaluronan is a major macromolecule of vitreous. It is a long, unbranched polymer of repeating disaccharide (glucuronic acid beta (1,3)-N-acetylglucosamine) moieties linked by beta 1-4 bonds. Hyaluronan is covalently linked to a protein core, to form a proteoglycan. It plays a pivotal role in stabilizing the vitreous gel. Hyaluronidase cleaves glycosidic bonds of hyaluronic acid and, to a variable degree, other acid mucopolysaccharides of the connective tissue. Dissolution of the hyaluronic acid and collagen complex results in decreased viscosity of the extracellular matrix. This in turn increases the diffusion rate of erythrocytes and exudates along with phagocytes through the vitreous and facilitates red blood cell lysis and phagocytosis.
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PMID:Hyaluronidase for pharmacologic vitreolysis. 1949 48

Mucopolysaccharidosis IVA is an autosomal recessive condition caused by mutations in the GALNS gene, which encodes N-acetylgalactosamine-6-sulfatase, also called galactosamine-6-sulfatase (GALNS). A reduction in or absence of effective GALNS leads to faulty catabolism of keratan sulfate and chondroitin-6-sulfate within the lysosome; their accumulation causes cell, tissue, and organ dysfunction. The connective tissue, cartilage, ligaments, and bone of patients with Morquio A syndrome are particularly affected. Patients with Morquio A syndrome are at high risk of neurological complications because of their skeletal abnormalities; many patients are in danger of cervical myelopathy due to odontoid hypoplasia and ligamentous laxity leading to atlantoaxial subluxation. The multisystemic involvement of patients with Morquio A syndrome requires treatment by multidisciplinary teams; not all members of these teams may be aware of the potential for subluxation and quadriparesis. A multinational, multidisciplinary panel of 10 skeletal dysplasia or Morquio A syndrome specialists convened in Miami, FL on December 7 and 8, 2012 to develop consensus recommendations for early identification and effective management of spinal cord compression, for anesthesia and surgical best practices, and for effectual cardiac and respiratory management in patients with Morquio A syndrome. The target audience for these recommendations includes any physician who may encounter a patient with Morquio A syndrome, however doctors who do not have access to the full spectrum of specialists and resources needed to support patients with Morquio A syndrome should attempt to refer patients to a center that does. Physicians who manage Morquio A syndrome or comorbid conditions within specialty centers should review these expert panel recommendations and fully understand the implications of spinal cord instability for their own practices.
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PMID:Diagnostic evaluation, monitoring, and perioperative management of spinal cord compression in patients with Morquio syndrome. 2549 28