Chondroitinase treatment

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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

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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.

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<span class="mw-page-title-main">Stephen Brendan McMahon</span> British neuroscientist (1954–2021)

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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.
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