Chondroitinase treatment

Last updated
Chondroitinase treatment
Specialty neurology

Chondroitinase treatment is a treatment of proteoglycans, a protein in the fluid among cells where (among other things) they affect neural activity (communication, plasticity). [1] Chondroitinase treatment has been shown to allow adults vision to be restored as far as ocular dominance is concerned. [2] Moreover, there is some evidence that Chondroitinase could be used for the treatment of spinal injuries. [3]

In addition, the enzyme that is used in the chondroitinase treatment, chondroitinase ABC, derives from the bacterium Proteus vulgaris. [4] In recent years, pre-clinical research involving the chondroitinase ABC enzyme has been mainly directed towards utilizing it as a way of treating spinal cord injuries in test animals using viral vectors. [5] In general, the way chondroitinase ABC works in vivo is it cleaves off the side chains of molecules known as chondroitin sulfate proteoglycans (CSPGs) which are over produced by glial cells in the central nervous system when a spinal injury occurs. [4] [5] When chondroitin sulfate proteoglycans are bonded to their side chains called chondroitin sulfate glycosaminoglycans, these molecules are known to prevent neural restoration to the damaged region of the central nervous system because they form glial scar tissue which inhibits both neuroplasticity and repair of damaged axons. [5] [6] However, when the side chains of the chondroitin sulfate proteoglycans are cleaved by chondroitinase ABC, this promotes the damaged region of the CNS to recover from the spinal cord injury. [4]

It has recently been proposed that chondroitinase treatment promotes plasticity by activation of Tropomyosin receptor kinase B, receptor for Brain-derived neurotrophic factor and a major plasticity orchestrator in the brain. [7] Cleavage of CSPGs by chondroitinase ABC leads to inactivation of PTPRS, the membrane receptor for CSPGs and a phosphatase that inactivates TRKB under normal physiological conditions, which subsequently promotes TRKB phosphorylation and activation of neuroplasticity.[ citation needed ]

See also

Related Research Articles

<span class="mw-page-title-main">Oligodendrocyte</span> Neural cell type

Oligodendrocytes, or oligodendroglia, are a type of neuroglia whose main functions are to provide support and insulation to axons in the central nervous system of jawed vertebrates, equivalent to the function performed by Schwann cells in the peripheral nervous system. Oligodendrocytes do this by creating the myelin sheath. A single oligodendrocyte can extend its processes to 50 axons, wrapping approximately 1 μm of myelin sheath around each axon; Schwann cells, on the other hand, can wrap around only one axon. Each oligodendrocyte forms one segment of myelin for several adjacent axons.

<span class="mw-page-title-main">Astrogliosis</span> Increase in astrocytes in response to brain injury

Astrogliosis is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons from central nervous system (CNS) trauma, infection, ischemia, stroke, autoimmune responses or neurodegenerative disease. In healthy neural tissue, astrocytes play critical roles in energy provision, regulation of blood flow, homeostasis of extracellular fluid, homeostasis of ions and transmitters, regulation of synapse function and synaptic remodeling. Astrogliosis changes the molecular expression and morphology of astrocytes, in response to infection for example, in severe cases causing glial scar formation that may inhibit axon regeneration.

Oligodendrocyte progenitor cells (OPCs), also known as oligodendrocyte precursor cells, NG2-glia, O2A cells, or polydendrocytes, are a subtype of glia in the central nervous system named for their essential role as precursors to oligodendrocytes. They are typically identified in the human by co-expression of PDGFRA and CSPG4.

<span class="mw-page-title-main">Versican</span> Protein-coding gene in the species Homo sapiens

Versican is a large extracellular matrix proteoglycan that is present in a variety of human tissues. It is encoded by the VCAN gene.

<span class="mw-page-title-main">Neuroimmune system</span>

The neuroimmune system is a system of structures and processes involving the biochemical and electrophysiological interactions between the nervous system and immune system which protect neurons from pathogens. It serves to protect neurons against disease by maintaining selectively permeable barriers, mediating neuroinflammation and wound healing in damaged neurons, and mobilizing host defenses against pathogens.

<span class="mw-page-title-main">Perlecan</span>

Perlecan (PLC) also known as basement membrane-specific heparan sulfate proteoglycan core protein (HSPG) or heparan sulfate proteoglycan 2 (HSPG2), is a protein that in humans is encoded by the HSPG2 gene. The HSPG2 gene codes for a 4,391 amino acid protein with a molecular weight of 468,829. It is one of the largest known proteins.

<span class="mw-page-title-main">Aggrecan</span>

Aggrecan (ACAN), also known as cartilage-specific proteoglycan core protein (CSPCP) or chondroitin sulfate proteoglycan 1, is a protein that in humans is encoded by the ACAN gene. This gene is a member of the lectican (chondroitin sulfate proteoglycan) family. The encoded protein is an integral part of the extracellular matrix in cartilagenous tissue and it withstands compression in cartilage.

Neuroregeneration involves the regrowth or repair of nervous tissues, cells or cell products. Neuroregenerative mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous system (PNS) and the central nervous system (CNS) by the functional mechanisms involved, especially in the extent and speed of repair. When an axon is damaged, the distal segment undergoes Wallerian degeneration, losing its myelin sheath. The proximal segment can either die by apoptosis or undergo the chromatolytic reaction, which is an attempt at repair. In the CNS, synaptic stripping occurs as glial foot processes invade the dead synapse.

<span class="mw-page-title-main">Syndecan 1</span> Protein which in humans is encoded by the SDC1 gene

Syndecan 1 is a protein which in humans is encoded by the SDC1 gene. The protein is a transmembrane heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecan-1 protein functions as an integral membrane protein and participates in cell proliferation, cell migration and cell-matrix interactions via its receptor for extracellular matrix proteins. Syndecan-1 is a sponge for growth factors and chemokines, with binding largely via heparan sulfate chains. The syndecans mediate cell binding, cell signaling, and cytoskeletal organization and syndecan receptors are required for internalization of the HIV-1 tat protein.

<span class="mw-page-title-main">Glial scar</span> Mass formed in response to injury to the nervous system

A glial scar formation (gliosis) is a reactive cellular process involving astrogliosis that occurs after injury to the central nervous system. As with scarring in other organs and tissues, the glial scar is the body's mechanism to protect and begin the healing process in the nervous system.

<span class="mw-page-title-main">Perineuronal net</span>

Perineuronal nets (PNNs) are specialized extracellular matrix structures responsible for synaptic stabilization in the adult brain. PNNs are found around certain neuron cell bodies and proximal neurites in the central nervous system. PNNs play a critical role in the closure of the childhood critical period, and their digestion can cause restored critical period-like synaptic plasticity in the adult brain. They are largely negatively charged and composed of chondroitin sulfate proteoglycans, molecules that play a key role in development and plasticity during postnatal development and in the adult.

<span class="mw-page-title-main">CSPG4</span> Protein-coding gene in the species Homo sapiens

Chondroitin sulfate proteoglycan 4, also known as melanoma-associated chondroitin sulfate proteoglycan (MCSP) or neuron-glial antigen 2 (NG2), is a chondroitin sulfate proteoglycan that in humans is encoded by the CSPG4 gene.

<span class="mw-page-title-main">XYLT1</span> Protein-coding gene in the species Homo sapiens

Xylosyltransferase 1 is an enzyme that in humans is encoded by the XYLT1 gene.

<span class="mw-page-title-main">CSPG5</span> Protein-coding gene in the species Homo sapiens

Chondroitin sulfate proteoglycan 5 is a protein that in humans is encoded by the CSPG5 gene.

<span class="mw-page-title-main">Chondroitin sulfate proteoglycan</span>

Chondroitin sulfate proteoglycans (CSPGs) are proteoglycans consisting of a protein core and a chondroitin sulfate side chain. They are known to be structural components of a variety of human tissues, including cartilage, and also play key roles in neural development and glial scar formation. They are known to be involved in certain cell processes, such as cell adhesion, cell growth, receptor binding, cell migration, and interaction with other extracellular matrix constituents. They are also known to interact with laminin, fibronectin, tenascin, and collagen. CSPGs are generally secreted from cells.

Neural/glial antigen 2, or NG2, is a rat integral membrane proteoglycan found in the plasma membrane of many diverse cell types. Homologous proteins in other species include human CSPG4, also known as melanoma-associated chondroitin sulfate proteoglycan (MCSP), Mouse AN2, and Sea urchin ECM3. This single-pass transmembrane molecule may be plasma membrane-bound or secreted and associated with the extracellular matrix. It is believed to play a role in functions such as cell adhesion, cell-cell and cell-ECM communication, migration and metastasis, proliferation, and axonal growth, guidance and regeneration. NG2-positive cells include oligodendrocyte progenitor cells (OPCs) and other progenitor cell populations, such as chondroblasts, myoblasts, and pericytes, as well as several different tumors including glioblastoma multiforme and melanoma.

<span class="mw-page-title-main">Center for Neurotechnology</span>

The Center for Neurotechnology (CNT) is an Engineering Research Center funded by the National Science Foundation to create devices to restore the body's capabilities for sensation and movement. The National Science Foundation has awarded the CNT $~30 million since 2011.

Chondroitin ABC lyase is an enzyme with systematic name chondroitin ABC lyase. This enzyme catalyses the following chemical reaction

Lorne Mendell is a neurobiologist currently employed as a distinguished professor in the department of neurobiology and behavior at Stony Brook University in New York. His research focuses primarily on neurotrophins in neonatal and adult mammals, and on the neuroplasticity of the mammalian spinal cord. His research interests lie in other areas including pain, nerve wind-up, and specifically the neurotrophin NT-3. He has contributed to the growing pool of knowledge of axonal development and regeneration of immature and mature neurons. He has been a part of the search for novel treatments for spinal cord injuries and continues to study neurotrophins to determine their effects on neuronal plasticity. He served a term as president of the Society of Neuroscience during 1997–1998.

Sandra M. Garraway is a Canadian-American neuroscientist and assistant professor of physiology in the Department of Physiology at Emory University School of Medicine in Atlanta, Georgia. Garraway is the director of the Emory Multiplex Immunoassay Core (EMIC) where she assists researchers from both academia and industry to perform, analyze, and interpret their multiplexed immunoassays. Garraway studies the neural mechanisms of spinal nociceptive pain after spinal cord injury and as a postdoctoral researcher she discovered roles for both BDNF and ERK2 in pain sensitization and developed novel siRNA technology to inhibit ERK2 as a treatment for pain.

References

  1. Cambridge Centre for Brain Repair, School of Clinical Medicine, Cambridge Centre for Brain Repair. Plasticity and the extracellular matrix. Archived 2007-12-03 at the Wayback Machine
  2. Hensch TK (2005). "Critical period mechanisms in developing visual cortex". Neural Development. Current Topics in Developmental Biology. Vol. 69. pp. 215–37. doi:10.1016/S0070-2153(05)69008-4. ISBN   9780121531690. PMID   16243601.
  3. "Spinal injury regeneration hope". BBC NEWS, online. 17 February 2008. Retrieved 2009-12-31.
  4. 1 2 3 Zhao RR, Fawcett JW (August 2013). "Combination treatment with chondroitinase ABC in spinal cord injury--breaking the barrier". Neuroscience Bulletin. 29 (4): 477–83. doi:10.1007/s12264-013-1359-2. PMC   5561941 . PMID   23839053.
  5. 1 2 3 Burnside ER, De Winter F, Didangelos A, James ND, Andreica EC, Layard-Horsfall H, Muir EM, Verhaagen J, Bradbury EJ (August 2018). "Immune-evasive gene switch enables regulated delivery of chondroitinase after spinal cord injury". Brain. 141 (8): 2362–2381. doi:10.1093/brain/awy158. PMC   6061881 . PMID   29912283.
  6. Bradbury EJ, Carter LM (March 2011). "Manipulating the glial scar: chondroitinase ABC as a therapy for spinal cord injury". Brain Research Bulletin. 84 (4–5): 306–16. doi:10.1016/j.brainresbull.2010.06.015. PMID   20620201. S2CID   10605553.
  7. Lesnikova, Angelina; Casarotto, Plinio Cabrera; Fred, Senem Merve; Voipio, Mikko; Winkel, Frederike; Steinzeig, Anna; Antila, Hanna; Umemori, Juzoh; Biojone, Caroline; Castrén, Eero (2020-12-08). "Chondroitinase and antidepressants promote plasticity by releasing TRKB from dephosphorylating control of PTPσ in parvalbumin neurons". Journal of Neuroscience. 41 (5): 972–980. doi: 10.1523/JNEUROSCI.2228-20.2020 . ISSN   0270-6474. PMC   7880295 . PMID   33293360.