Generic placeholder image

Current Drug Therapy


ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Review Article

Emerging Therapeutic Role of Chondroitinase (ChABC) in Neurological Disorders and Cancer

Author(s): Akshara Kumar, Aishi Biswas, Sree Lalitha Bojja, Kiran Kumar Kolathur* and Subrahmanyam M. Volety

Volume 17, Issue 3, 2022

Published on: 10 June, 2022

Page: [160 - 170] Pages: 11

DOI: 10.2174/1574885517666220331151619

Price: $65


Proteoglycans are essential biomacromolecules that participate in matrix structure and organization, cell proliferation and migration, and cell surface signal transduction. However, their roles in physiology, particularly in CNS, remain incompletely deciphered. Numerous studies highlight the elevated levels of chondroitin sulphate proteoglycans (CSPGs) in various diseases, like cancers, and neurological disorders, like spinal cord injury (SCI), traumatic brain damage, neurodegenerative diseases, and are mainly implicated to hinder tissue repair. In such a context, chondroitinase ABC (ChABC), a therapeutic enzyme, has shown immense hope to treat these diseases in several preclinical studies, primarily attributed to the digestion of the side chains of the proteoglycan chondroitin sulphate (CS) molecule. Despite extensive research, the progress in evolution of the concept of therapeutic targeting of proteoglycans is still in its infancy. This review thus provides fresh insights into the emerging therapeutic applications of ChABC in various diseases apart from SCI and the underlying mechanisms.

Keywords: Proteoglycans, chondroitin sulphate proteoglycans, perineuronal nets, neurodegenerative, cancer, chondroitinase ABC (ChABC).

Graphical Abstract
Hardingham TE, Fosang AJ. Proteoglycans: Many forms and many functions. FASEB J 1992; 6(3): 861-70.
[] [PMID: 1740236]
Perrimon N, Bernfield M. Cellular functions of proteoglycans-An overview. Semin Cell Dev Biol 2001; 12(2): 65-7.
[] [PMID: 11292371]
Kjellén L, Lindahl U. Proteoglycans: Structures and interactions. Annu Rev Biochem 1991; 60: 443-75.
Kasinathan N, Volety SM, Josyula VR. Chondroitinase: A promising therapeutic enzyme. Crit Rev Microbiol 2016; 42: 474-84.
Webb DJ, Parsons JT, Horwitz AF. Adhesion assembly, disassembly and turnover in migrating cells -- over and over and over again. Nat Cell Biol 2002; 4(4): E97-E100.
[] [PMID: 11944043]
Heindryckx F, Li J-P. Role of proteoglycans in neuro-inflammation and central nervous system fibrosis. Matrix Biol 2018; 68-69: 589-601.
[] [PMID: 29382609]
Sorg BA, Berretta S, Blacktop JM, et al. Casting a wide net: Role of perineuronal nets in neural plasticity. J Neurosci 2016; 36(45): 11459-68.
[] [PMID: 27911749]
Muir E, De Winter F, Verhaagen J, Fawcett J. Recent advances in the therapeutic uses of chondroitinase ABC. Exp Neurol 2019; 321: 113032.
Gallagher JT. The extended family of proteoglycans: Social residents of the pericellular zone. Curr Opin Cell Biol 1989; 1(6): 1201-18.
[] [PMID: 2517581]
Soares da Costa D, Reis RL, Pashkuleva I. Sulfation of glycosaminoglycans and its implications in human health and disorders. Annu Rev Biomed Eng 2017; 19(1): 1-26.
[] [PMID: 28226217]
Asimakopoulou AP, Theocharis AD, Tzanakakis GN, Karamanos NK. The biological role of chondroitin sulfate in cancer and chondroitin-based anticancer agents. In Vivo (Brooklyn) 2008; 22(3): 385-90.
Wegrowski Y, Maquart F-X. Chondroitin sulfate proteoglycans in tumor progression. Adv Pharmacol 2006; 53: 297-321.
[] [PMID: 17239772]
Cattaruzza S, Perris R. Proteoglycan control of cell movement during wound healing and cancer spreading. Matrix Biol 2005; 24(6): 400-17.
[] [PMID: 16055321]
Afratis N, Gialeli C, Nikitovic D, et al. Glycosaminoglycans: Key players in cancer cell biology and treatment. FEBS J 2012; 279(7): 1177-97.
[] [PMID: 22333131]
Bradbury EJ, Moon LDF, Popat RJ, et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 2002; 416(6881): 636-40.
[] [PMID: 11948352]
Sivak WN, White JD, Bliley JM, et al. Delivery of chondroitinase ABC and glial cell line-derived neurotrophic factor from silk fibroin conduits enhances peripheral nerve regeneration. J Tissue Eng Regen Med 2017; 11(3): 733-42.
[] [PMID: 25424415]
Gardner RT, Habecker BA. Infarct-derived chondroitin sulfate proteoglycans prevent sympathetic reinnervation after cardiac ischemia-reperfusion injury. J Neurosci 2013; 33(17): 7175-83.
Lu P, Takai K, Weaver VM, Werb Z. Extracellular Matrix degradation and remodeling in development and disease. Cold Spring Harb Perspect Biol 2011; 3(12): a005058.
Schwartz NB, Domowicz MS. Proteoglycans in brain development and pathogenesis. FEBS Lett 2018; 592(23): 3791-805.
[] [PMID: 29513405]
Avram S, Shaposhnikov S, Buiu C, Mernea M. Chondroitin sulfate proteoglycans: Structure-function relationship with implication in neural development and brain disorders. BioMed Res Int 2014; 2014: 642798.
[] [PMID: 24955366]
Fawcett JW, Oohashi T, Pizzorusso T. The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function. Nat Rev Neurosci 2019; 20: 451-65.
McRae PA, Porter BE. The perineuronal net component of the extracellular matrix in plasticity and epilepsy. Neurochem Int 2012; 61: 963-72.
Morris NP, Henderson Z. Perineuronal nets ensheath fast spiking, parvalbumin-immunoreactive neurons in the medial septum/diagonal band complex. Eur J Neurosci 2000; 12(3): 828-38.
[] [PMID: 10762312]
Härtig W, Singer A, Grosche J, Brauer K, Ottersen OP, Brückner G. Perineuronal nets in the rat medial nucleus of the trapezoid body surround neurons immunoreactive for various amino acids, calcium-binding proteins and the potassium channel subunit Kv3.1b. Brain Res 2001; 899(1-2): 123-33.
[] [PMID: 11311873]
Köppe G, Brückner G, Härtig W, Delpech B, Bigl V. Characterization of proteoglycan-containing perineuronal nets by enzymatic treatments of rat brain sections. Histochem J 1997; 29(1): 11-20.
[] [PMID: 9088941]
Kwok JCF, Carulli D, Fawcett JW. In vitro modeling of perineuronal nets: Hyaluronan synthase and link protein are necessary for their formation and integrity. J Neurochem 2010; 114(5): 1447-59.
[] [PMID: 20584105]
Wang D, Fawcett J. The perineuronal net and the control of CNS plasticity. Cell Tissue Res 2012; 349(1): 147-60.
[] [PMID: 22437874]
Spicer AP, Joo A, Bowling RA Jr. A hyaluronan binding link protein gene family whose members are physically linked adjacent to chondroitin sulfate proteoglycan core protein genes: The missing links. J Biol Chem 2003; 278(23): 21083-91.
[] [PMID: 12663660]
Lundell A, Olin AI, Mörgelin M, al-Karadaghi S, Aspberg A, Logan DT. Structural basis for interactions between tenascins and lectican C-type lectin domains: Evidence for a crosslinking role for tenascins. Structure 2004; 12(8): 1495-506.
[] [PMID: 15296743]
Hatten ME, Liem RKH, Shelanski ML, Mason CA. Astroglia in CNS injury. Glia 1991; 4(2): 233-43.
[] [PMID: 1827781]
Chen ZJ, Negra M, Levine A, Ughrin Y, Levine JM. Oligodendrocyte precursor cells: Reactive cells that inhibit axon growth and regeneration. J Neurocytol 2002; 31(6-7): 481.
Fawcett JW, Asher RA. The glial scar and central nervous system repair. Brain Res Bull 1999; 49(6): 377-91.
[] [PMID: 10483914]
Davies SJA, Goucher DR, Doller C, Silver J. Robust regeneration of adult sensory axons in degenerating white matter of the adult rat spinal cord. J Neurosci 1999; 19(14): 5810-22.
[] [PMID: 10407022]
Asher RA, Morgenstern DA, Fidler PS, et al. Neurocan is upregulated in injured brain and in cytokine-treated astrocytes. J Neurosci 2000; 20(7): 2427-38.
[] [PMID: 10729323]
Chung KY, Taylor JSH, Shum DKY, Chan SO. Axon routing at the optic chiasm after enzymatic removal of chondroitin sulfate in mouse embryos. Development 2000; 127(12): 2673-83.
[] [PMID: 10821765]
Yick LW, Wu W, So KF, Yip HK, Shum DK. Chondroitinase ABC promotes axonal regeneration of Clarke’s neurons after spinal cord injury. Neuroreport 2000; 11(5): 1063-7.
[] [PMID: 10790883]
Moon LDF, Asher RA, Rhodes KE, Fawcett JW. Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC. Nat Neurosci 2001; 4(5): 465-6.
[] [PMID: 11319553]
Gogolla N, Caroni P, Lüthi A, Herry C. Perineuronal nets protect fear memories from erasure. Science (80-) 2009; 325(5945): 1258-61.
Hylin MJ, Orsi SA, Moore AN, Dash PK. Disruption of the perineuronal net in the hippocampus or medial prefrontal cortex impairs fear conditioning. Learn Mem 2013; 20(5): 267-73.
[] [PMID: 23592037]
van ’t Spijker HM, Kwok JCF. A sweet talk: The molecular systems of perineuronal nets in controlling neuronal communication. Front Integr Nuerosci 2017; 11: 33.
[] [PMID: 29249944]
Shi W, Wei X, Wang X, et al. Perineuronal nets protect long-term memory by limiting activity-dependent inhibition from parvalbumin interneurons. Proc Natl Acad Sci 2019; 116(52): 27063-73.
Banerjee SB, Gutzeit VA, Baman J, et al. Perineuronal nets in the adult sensory cortex are necessary for fear learning. Neuron 2017; 95(1): 169-179.e3.
Xue Y-X, Xue L-F, Liu J-F, et al. Depletion of perineuronal nets in the amygdala to enhance the erasure of drug memories. J Neurosci 2014; 34(19): 6647-58.
[] [PMID: 24806690]
Christensen AC, Lensjø KK, Lepperød ME, et al. Perineuronal nets stabilize the grid cell network. Nat Commun 2021; 12(1): 253.
[] [PMID: 33431847]
Pizzorusso T, Medini P, Berardi N, Chierzi S, Fawcett JW, Maffei L. Reactivation of ocular dominance plasticity in the adult visual cortex. Science (80- ) 2002; 298(5596): 1248-51.
Lesnikova A, Casarotto PC, Fred SM, et al. Chondroitinase and antidepressants promote plasticity by releasing TRKB from dephosphorylating control of ptpσ in parvalbumin neurons. J Neurosci 2021; 41(5): 972-80.
[] [PMID: 33293360]
Umemori J, Winkel F, Didio G, Llach Pou M, Castrén E. iPlasticity: Induced juvenile-like plasticity in the adult brain as a mechanism of antidepressants. Psychiatry Clin Neurosci 2018; 72: 633-53.
Castrén E, Antila H. Neuronal plasticity and neurotrophic factors in drug responses. Mol Psychiatry 2017; 22: 1085-95.
Minichiello L, Korte M, Wolfer D, et al. Essential role for TrkB receptors in hippocampus-mediated learning. Neuron 1999; 24(2): 401-14.
[] [PMID: 10571233]
Smith MA. Alzheimer disease. Int Rev Neurobiol 1998; 42: 1-54.
[] [PMID: 9476170]
Hyman BT. AD cell specific pathology. Science 1984; 225: 1168-70.
Querfurth HW, Laferla FM. Alzheimer’s disease. N Engl J Med 2018; 329-44.
Morra JH, Tu Z, Apostolova LG, et al. Alzheimer’s Disease Neuroimaging Initiative. Automated 3D mapping of hippocampal atrophy and its clinical correlates in 400 subjects with Alzheimer’s disease, mild cognitive impairment, and elderly controls. Hum Brain Mapp 2009; 30(9): 2766-88.
[] [PMID: 19172649]
Végh MJ, Heldring CM, Kamphuis W, et al. Reducing hippocampal extracellular matrix reverses early memory deficits in a mouse model of Alzheimer’s disease. Acta Neuropathol Commun 2014; 2(1): 76.
[] [PMID: 24974208]
Yang S, Cacquevel M, Saksida LM, et al. Perineuronal net digestion with chondroitinase restores memory in mice with tau pathology. Exp Neurol 2015; 265: 48-58.
[] [PMID: 25483398]
Romberg C, Yang S, Melani R, et al. Depletion of perineuronal nets enhances recognition memory and long-term depression in the perirhinal cortex. J Neurosci 2013; 33(16): 7057-65.
[] [PMID: 23595763]
Matsui F, Nishizuka M, Yasuda Y, Aono S, Watanabe E, Oohira A. Occurrence of a N-terminal proteolytic fragment of neurocan, not a C-terminal half, in a perineuronal net in the adult rat cerebrum. Brain Res 1998; 790(1-2): 45-51.
[] [PMID: 9593817]
Carulli D, Rhodes KE, Brown DJ, et al. Composition of perineuronal nets in the adult rat cerebellum and the cellular origin of their components. J Comp Neurol 2006; 494(4): 559-77.
[] [PMID: 16374793]
Ruoslahti E. Brain extracellular matrix. Glycobiology 1996; 6(5): 489-92.
[] [PMID: 8877368]
Howell MD, Bailey LA, Cozart MA, Gannon BM, Gottschall PE. Hippocampal administration of chondroitinase ABC increases plaque-adjacent synaptic marker and diminishes amyloid burden in aged APPswe/PS1dE9 mice. Acta Neuropathol Commun 2015; 3(1): 54.
[] [PMID: 26337292]
Levy AD, Omar MH, Koleske AJ. Extracellular matrix control of dendritic spine and synapse structure and plasticity in adulthood. Front Neuroanat 2014; 8: 116.
[] [PMID: 25368556]
Lang AE, Lozano AMP. Parkinson’s disease. Second of two parts. N Engl J Med 1998; 339(16): 1130-43.
[] [PMID: 9770561]
DeWitt DA, Richey PL, Praprotnik D, Silver J, Perry G. Chondroitin sulfate proteoglycans are a common component of neuronal inclusions and astrocytic reaction in neurodegenerative diseases. Brain Res 1994; 656(1): 205-9.
[] [PMID: 7804839]
Crespo D, Asher RA, Lin R, Rhodes KE, Fawcett JW. How does chondroitinase promote functional recovery in the damaged CNS? Exp Neurol 2007; 206(2): 159-71.
[] [PMID: 17572406]
Kauhausen JA, Thompson LH, Parish CL. Chondroitinase improves midbrain pathway reconstruction by transplanted dopamine progenitors in Parkinsonian mice. Mol Cell Neurosci 2015; 69: 22-9.
[] [PMID: 26463051]
Fletcher EJR, Moon LDF, Duty S. Chondroitinase ABC reduces dopaminergic nigral cell death and striatal terminal loss in a 6-hydroxydopamine partial lesion mouse model of Parkinson’s disease. BMC Neurosci 2019; 20(1): 61.
[] [PMID: 31862005]
Lassmann H. Multiple sclerosis pathology. Cold Spring Harb Perspect Med 2018; 8(3): 1-15.
[] [PMID: 29358320]
Lau LW, Keough MB, Haylock-Jacobs S, et al. Chondroitin sulfate proteoglycans in demyelinated lesions impair remyelination. Ann Neurol 2012; 72(3): 419-32.
[] [PMID: 23034914]
Kotter MR, Stadelmann C, Hartung H-P. Enhancing remyelination in disease--can we wrap it up? Brain 2011; 134(Pt 7): 1882-900.
[] [PMID: 21507994]
Back SA, Tuohy TMF, Chen H, et al. Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation. Nat Med 2005; 11(9): 966-72.
[] [PMID: 16086023]
Sloane JA, Batt C, Ma Y, Harris ZM, Trapp B, Vartanian T. Hyaluronan blocks oligodendrocyte progenitor maturation and remyelination through TLR2. Proc Natl Acad Sci 2010; 107(25): 11555-60.
Sobel RA, Ahmed AS. White matter extracellular matrix chondroitin sulfate/dermatan sulfate proteoglycans in multiple sclerosis. J Neuropathol Exp Neurol 2001; 60(12): 1198-207.
[] [PMID: 11764092]
Siebert JR, Osterhout DJ. The inhibitory effects of chondroitin sulfate proteoglycans on oligodendrocytes. J Neurochem 2011; 119(1): 176-88.
[] [PMID: 21848846]
Keough MB, Rogers JA, Zhang P, et al. An inhibitor of chondroitin sulfate proteoglycan synthesis promotes central nervous system remyelination. Nat Commun 2016; 7(1): 11312.
[] [PMID: 27115988]
Warford JR, Lamport AC, Clements DR, et al. Surfen, a proteoglycan binding agent, reduces inflammation but inhibits remyelination in murine models of Multiple Sclerosis. Acta Neuropathol Commun 2018; 6(1): 4.
[] [PMID: 29301568]
Stephenson EL, Zhang P, Ghorbani S, et al. Targeting the chondroitin sulfate proteoglycans: Evaluating fluorinated glucosamines and xylosides in screens pertinent to multiple sclerosis. ACS Cent Sci 2019; 5(7): 1223-34.
Buttery PC. ffrench-Constant C. Laminin-2/integrin interactions enhance myelin membrane formation by oligodendrocytes. Mol Cell Neurosci 1999; 14(3): 199-212.
[] [PMID: 10576890]
Ughrin YM, Chen ZJ, Levine JM. Multiple regions of the NG2 proteoglycan inhibit neurite growth and induce growth cone collapse. J Neurosci 2003; 23(1): 175-86.
Lalitha S, Minz RW, Medhi B. Understanding the controversial drug targets in epilepsy and pharmacoresistant epilepsy. Rev Neurosci 2018; 29(3): 333-45.
[] [PMID: 29211683]
Rankin-Gee EK, McRae PA, Baranov E, Rogers S, Wandrey L, Porter BE. Perineuronal net degradation in epilepsy. Epilepsia 2015; 56(7): 1124-33.
[] [PMID: 26032766]
Tewari BP, Chaunsali L, Campbell SL, Patel DC, Goode AE, Sontheimer H. Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy. Nat Commun 2018; 9(1): 4724.
[] [PMID: 30413686]
Chen W, Li YS, Gao J, Lin XY, Li XH. AMPA receptor antagonist NBQX decreased seizures by normalization of perineuronal nets. PLoS One 2016; 11(11): 166672.
Prabhakar V, Sasisekharan RBT-A. The biosynthesis and catabolism of galactosaminoglycans. In: Chondroitin sulfate: Structure, role and pharmacological activity. USA: Academic Press 2006; pp. 69-115.
Denholm EM, Lin YQ, Silver PJ. Anti-tumor activities of chondroitinase AC and chondroitinase B: Inhibition of angiogenesis, proliferation and invasion. Eur J Pharmacol 2001; 416(3): 213-21.
[] [PMID: 11290371]
Garrigues HJ, Lark MW, Lara S, Hellström I, Hellström KE, Wight TN. The melanoma proteoglycan: Restricted expression on microspikes, a specific microdomain of the cell surface. J Cell Biol 1986; 103(5): 1699-710.
[] [PMID: 2430975]
Faassen AE, Schrager JA, Klein DJ, Oegema TR, Couchman JR, McCarthy JB. A cell surface chondroitin sulfate proteoglycan, immunologically related to CD44, is involved in type I collagen-mediated melanoma cell motility and invasion. J Cell Biol 1992; 116(2): 521-31.
[] [PMID: 1730766]
Henke CA, Roongta U, Mickelson DJ, Knutson JR, McCarthy JB. CD44-related chondroitin sulfate proteoglycan, a cell surface receptor implicated with tumor cell invasion, mediates endothelial cell migration on fibrinogen and invasion into a fibrin matrix. J Clin Invest 1996; 97(11): 2541-52.
[] [PMID: 8647947]
Takeuchi J. Effect of chondroitinases on the growth of solid Ehrlich ascites tumour. Br J Cancer 1972; 26(2): 115-9.
[] [PMID: 5038324]
Viapiano MS, Matthews RT. From barriers to bridges: Chondroitin sulfate proteoglycans in neuropathology. Trends Mol Med 2006; 12(10): 488-96.
[] [PMID: 16962376]
Wade A, Robinson AE, Engler JR, Petritsch C, James CD, Phillips JJ. Proteoglycans and their roles in brain cancer. FEBS J 2013; 280(10): 2399-417.
Pan H, Xue W, Zhao W, Schachner M. Expression and function of chondroitin 4-sulfate and chondroitin 6-sulfate in human glioma. FASEB J 2020; 34(2): 2853-68.
[] [PMID: 31908019]
Natori T, Nagai K. Endoplasmic reticulum stress upregulates the chondroitin sulfate level which thus prevents neurite extension in C6 glioma cells and primary cultured astrocytes. Cell Mol Neurobiol 2008; 28(6): 857-66.
[] [PMID: 18264755]
Kim Y, Lee HG, Dmitrieva N, et al. Choindroitinase ABC I-mediated enhancement of oncolytic virus spread and anti tumor efficacy: A mathematical model. PLoS One 2014; 9(7): e102499.
[] [PMID: 25047810]
Jaime-Ramirez AC, Dmitrieva N, Yoo JY, et al. Humanized chondroitinase ABC sensitizes glioblastoma cells to temozolomide. J Gene Med 2017; 19(3): e2942.
[] [PMID: 28087981]
Dwyer CA, Bi WL, Viapiano MS, Matthews RT. Brevican knockdown reduces late-stage glioma tumor aggressiveness. J Neurooncol 2014; 120(1): 63-72.
[] [PMID: 25052349]
Korourian S, Siegel E, Kieber-Emmons T, Monzavi-Karbassi B. Expression analysis of carbohydrate antigens in ductal carcinoma in situ of the breast by lectin histochemistry. BMC Cancer 2008; 8(1): 136.
[] [PMID: 18479514]
Kawaguchi T. Cancer metastasis: Characterization and identification of the behavior of metastatic tumor cells and the cell adhesion molecules, including carbohydrates. Curr Drug Targets Cardiovasc Haematol Disord 2005; 5(1): 39-64.
[] [PMID: 15720223]
Gorelik E, Galili U, Raz A. On the role of cell surface carbohydrates and their binding proteins (lectins) in tumor metastasis. Cancer Metastasis Rev 2001; 20: 245-77.
Couldrey C, Green JE. Metastases: The glycan connection. Breast Cancer Res 2000; 2(5): 321-3.
[] [PMID: 11250723]
Mizumoto S, Watanabe M, Yamada S, Sugahara K. Expression of N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase involved in chondroitin sulfate synthesis is responsible for pulmonary metastasis. BioMed Res Int 2013; 2013: 656319.
Cooney CA, Jousheghany F, Yao-Borengasser A, et al. Chondroitin sulfates play a major role in breast cancer metastasis: A role for CSPG4 and CHST11 gene expression in forming surface P-selectin ligands in aggressive breast cancer cells. Breast Cancer Res 2011; 13(3): R58.
Prinz RD, Willis CM, Viloria-Petit A, Klüppel M. Elimination of breast tumor-associated chondroitin sulfate promotes metastasis. Genet Mol Res 2011; 10(4): 3901-13.
[] [PMID: 22183949]
Li F, Ten Dam GB, Murugan S, et al. Involvement of highly sulfated chondroitin sulfate in the metastasis of the Lewis lung carcinoma cells. J Biol Chem 2008; 283(49): 34294-304.
[] [PMID: 18930920]
Bowers CW, Baldwin C, Zigmond RE. Sympathetic reinnervation of the pineal gland after postganglionic nerve lesion does not restore normal pineal function. J Neurosci 1984; 4(8): 2010-5.
[] [PMID: 6470764]
Hill CE, Hirst GDS, Ngu MC, van Helden DF. Sympathetic postganglionic reinnervation of mesenteric arteries and enteric neurones of the ileum of the rat. J Auton Nerv Syst 1985; 14(4): 317-34.
[] [PMID: 4086723]
Day P, Alves N, Daniell E, et al. Targeting chondroitinase ABC to axons enhances the ability of chondroitinase to promote neurite outgrowth and sprouting. PLoS One 2020; 15(1): e0221851.
[] [PMID: 31961897]
Chen XR, Liao S-J, Ye LX, et al. Neuroprotective effect of chondroitinase ABC on primary and secondary brain injury after stroke in hypertensive rats. Brain Res 2014; 1543: 324-33.
[] [PMID: 24326094]
Yagi Y, Muroga E, Naitoh M, et al. An ex vivo model employing keloid-derived cell-seeded collagen sponges for therapy development. J Invest Dermatol 2013; 133(2): 386-93.
[] [PMID: 22951719]
Niessen FB, Spauwen PHM, Schalkwijk J, Kon M. On the nature of hypertrophic scars and keloids: A review. Plast Reconstr Surg 1999; 104(5): 1435-58.
[] [PMID: 10513931]
Ikeda M, Naitoh M, Kubota H, et al. Elastic fiber assembly is disrupted by excessive accumulation of chondroitin sulfate in the human dermal fibrotic disease, keloid. Biochem Biophys Res Commun 2009; 390(4): 1221-8.
[] [PMID: 19879246]
Ishiko T, Naitoh M, Kubota H, et al. Chondroitinase injection improves keloid pathology by reorganizing the extracellular matrix with regenerated elastic fibers. 2013; 40(5): 380-3.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy