Skip to main content

Proteoglycans of the Central Nervous System

  • Chapter
  • First Online:
Animal Lectins: Form, Function and Clinical Applications
  • 1486 Accesses

Abstract

The extracellular matrix (ECM) is a complex molecular framework that provides physical support to cells and tissues, while also providing signals for cell growth, migration, differentiation and survival. Proteoglycans, as part of the extracellular or cell-surface milieu of most tissues and organ systems, play important roles in morphogenesis by modulating cell-matrix or cell-cell interactions, cell adhesiveness, or by binding and presenting growth and differentiation factors. The basic concept, that specialized extracellular matrices rich in hyaluronan, chondroitin sulfate proteoglycans (CS-PG: aggrecan, versican, neurocan, brevican, phosphacan), link proteins and tenascins (Tn-R, Tn-C) can regulate cellular migration and axonal growth and thus, actively participate in the development and maturation of nervous system, has gained rapidly expanding experimental support (Zimmermann and Dours-Zimmermann 2008). The distribution of ECM molecules displays area-specific differences along the dorso-ventral axis, delimiting functionally and developmentally distinct areas. In gray matter, laminae I and II lack PNNs of extracellular matrix and contain low levels of chondroitin sulfate glycosaminoglycans (CS-GAGs), brevican, and tenascin-R, possibly favoring the maintenance of local neuroplastic properties. Conversely, CS-GAGs, brevican, and phosphacan were abundant, with numerous thick PNNs, in laminae III-VIII and X. Motor neurons (lamina IX), surrounded by PNNs, containd various amounts of CS-GAGs (Vitellaro-Zuccarello et al. 2007).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Akita K, Toda M, Hosoki Y et al (2004) Heparan sulphate proteoglycans interact with neurocan and promote neurite outgrowth from cerebellar granule cells. Biochem J 383:129–138

    PubMed  CAS  Google Scholar 

  • Alliel PM, Perin J-P, Jollès P, Bonnet FJ (2004) Testican, a multidomain testicular proteoglycan resembling modulators of cell social behaviour. Eur J Biochem 214:347–350

    Google Scholar 

  • Asher RA, Morgenstern DA, Shearer MC et al (2002) Versican is upregulated in CNS injury and is a product of oligodendrocyte lineage cells. J Neurosci 22:2225–2236

    PubMed  CAS  Google Scholar 

  • Aspberg A, Miura R, Bourdoulous S et al (1997) The C-type lectin domains of lecticans, a family of aggregating chondroitin sulfate proteoglycans, bind tenascin-R by protein-protein interactions independent of carbohydrate moiety. Proc Natl Acad Sci USA 94:10116–10121

    PubMed  CAS  Google Scholar 

  • Atoji Y, Yamamoto Y, Suzuki Y et al (1997) Immunohistochemical localization of neurocan in the lower auditory nuclei of the dog. Hear Res 110:200–208

    PubMed  CAS  Google Scholar 

  • Aya-ay J, Mayer J, Eakin AK et al (2005) The effect of hypoxic-ischemic brain injury in perinatal rats on the abundance and proteolysis of brevican and NG2. Exp Neurol 193:149–162

    PubMed  CAS  Google Scholar 

  • Barritt AW, Davies M, Marchand F et al (2006) Chondroitinase ABC promotes sprouting of intact and injured spinal systems after spinal cord injury. J Neurosci 26:10856–10867

    PubMed  CAS  Google Scholar 

  • Bbandtlow CE, Zzimmermann DR (2000) Proteoglycans in the developing brain: new conceptual insights for old proteins. Physiol Rev 80:1267–1290

    Google Scholar 

  • Beggah AT, Dours-Zimmermann MT, Barras FM et al (2005) Lesion-induced differential expression and cell association of neurocan, brevican, versican V1 and V2 in the mouse dorsal root entry zone. Neuroscience 133:749–762

    PubMed  CAS  Google Scholar 

  • Bekku Y, Su WD, Hirakawa S et al (2003) Molecular cloning of Bral2, a novel brain-specific link protein, and immunohistochemical colocalization with brevican in perineuronal nets. Mol Cell Neurosci 24:148–159

    PubMed  CAS  Google Scholar 

  • Bekku Y, Rauch U, Ninomiya Y, Oohashi T (2009) Brevican distinctively assembles extracellular components at the large diameter nodes of Ranvier in the CNS. J Neurochem 108:1266–1276

    PubMed  CAS  Google Scholar 

  • Bradbury EJ, Moon LD, Popat RJ et al (2002) Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 416:636–640

    PubMed  CAS  Google Scholar 

  • Brakebusch C, Seidenbecher CI, Asztely F et al (2002) Brevican-deficient mice display impaired hippocampal CA1 long-term potentiation but show no obvious deficits in learning and memory. Mol Cell Biol 22:7417–7427

    PubMed  CAS  Google Scholar 

  • Braunewell KH, Pesheva P, McCarthy JB et al (1995) Functional involvement of sciatic nerve-derived versican- and decorin-like molecules and other chondroitin sulphate proteoglycans in ECM-mediated cell adhesion and neurite outgrowth. Eur J Neurosci 7:805–814

    PubMed  CAS  Google Scholar 

  • Brückner G, Grosche J, Schmidt S et al (2000) Postnatal development of perineuronal nets in wild-type mice and in a mutant deficient in tenascin-R. J Comp Neurol 428:616–629

    PubMed  Google Scholar 

  • Brückner G, Grosche J, Hartlage-Rübsamen M et al (2003) Region and lamina-specific distribution of extracellular matrix proteoglycans, hyaluronan and tenascin-R in the mouse hippocampal formation. J Chem Neuroanat 26:37–50

    PubMed  Google Scholar 

  • Buss A, Pech K, Kakulas BA et al (2009) NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury. BMC Neurol 9:32

    PubMed  Google Scholar 

  • Carulli D, Rhodes KE, Fawcett JW (2007) Upregulation of aggrecan, link protein 1, and hyaluronan synthases during formation of perineuronal nets in the rat cerebellum. J Comp Neurol 501:83–94

    PubMed  CAS  Google Scholar 

  • Chan CC, Wong AK, Liu J et al (2007) ROCK inhibition with Y27632 activates astrocytes and increases their expression of neurite growth-inhibitory chondroitin sulfate proteoglycans. Glia 55:369–384

    PubMed  Google Scholar 

  • Clarris HJ, Rauch U, Key B (2000) Dynamic spatiotemporal expression patterns of neurocan and phosphacan indicate diverse roles in the developing and adult mouse olfactory system. J Comp Neurol 423:99–111

    PubMed  CAS  Google Scholar 

  • Cross AK, Haddock G, Surr J et al (2006) Differential expression of ADAMTS-1, -4, -5 and TIMP-3 in rat spinal cord at different stages of acute experimental autoimmune encephalomyelitis. J Autoimmun 26:16–23

    PubMed  CAS  Google Scholar 

  • Czipri M, Otto JM, Cs-Szabó G et al (2003) Genetic rescue of chondrodysplasia and the perinatal lethal effect of cartilage link protein deficiency. J Biol Chem 278:39214–39223

    PubMed  CAS  Google Scholar 

  • Davies JE, Tang X, Denning JW et al (2004) Decorin suppresses neurocan, brevican, phosphacan and NG2 expression and promotes axon growth across adult rat spinal cord injuries. Eur J Neurosci 19:1226–1242

    PubMed  Google Scholar 

  • Davies JE, Tang X, Bournat JC, Davies SJ (2006) Decorin promotes plasminogen/plasmin expression within acute spinal cord injuries and by adult microglia in vitro. J Neurotrauma 23:397–408

    PubMed  Google Scholar 

  • Day JM, Olin AI, Murdoch AD et al (2004) Alternative splicing in the aggrecan G3 domain influences binding interactions with tenascin-C and other extracellular matrix proteins. J Biol Chem 279:12511–12518

    PubMed  CAS  Google Scholar 

  • Deepa SS, Carulli D, Galtrey C et al (2006) Composition of perineuronal net extracellular matrix in rat brain: a different disaccharide composition for the net-associated proteoglycans. J Biol Chem 281:17789–17800

    PubMed  CAS  Google Scholar 

  • Deguchi K, Takaishi M, Hayashi T et al (2005) Expression of neurocan after transient middle cerebral artery occlusion in adult rat brain. Brain Res 1037:194–199

    PubMed  CAS  Google Scholar 

  • Dong Y, Han X, Xue Y et al (2004) Secreted brevican mRNA is expressed in the adult rat pituitary. Biochem Biophys Res Commun 314:745–748

    PubMed  CAS  Google Scholar 

  • Emerling DE, Lander AD (1996) Inhibitors and promoters of thalamic neuron adhesion and outgrowth in embryonic neocortex: functional association with chondroitin sulfate. Neuron 17:1089–1100

    PubMed  CAS  Google Scholar 

  • Engel M, Maurel P, Margolis RU, Margolis RK (1996) Chondroitin sulfate proteoglycans in the developing central nervous system. I. cellular sites of synthesis of neurocan and phosphacan. J Comp Neurol 366:34–43

    PubMed  CAS  Google Scholar 

  • Fawcett JW, Asher RA (1999) The glial scar and central nervous system repair. Brain Res Bull 49:377–391

    PubMed  CAS  Google Scholar 

  • Feng K, Arnold-Ammer I, Rauch U (2000) Neurocan is a heparin binding proteoglycan. Biochem Biophys Res Commun 272:449–455

    PubMed  CAS  Google Scholar 

  • Filbin MT (2003) Myelin-associated inhibitors of axonal regeneration in the adult mammalian CNS. Nat Rev Neurosci 4:703–713

    PubMed  CAS  Google Scholar 

  • Fosang AJ, Hardingham TE (1996) In: Comper WD (ed) Extracellular matrix, vol 1. Harwood Academic Publishers, Amsterdam

    Google Scholar 

  • Fuller ML, DeChant AK, Rothstein B et al (2007) Bone morphogenetic proteins promote gliosis in demyelinating spinal cord lesions. Ann Neurol 62:288–300

    PubMed  CAS  Google Scholar 

  • Galtrey CM, Kwok JC, Carulli D et al (2008) Distribution and synthesis of extracellular matrix proteoglycans, hyaluronan, link proteins and tenascin-R in the rat spinal cord. Eur J Neurosci 27:1373–1390

    PubMed  Google Scholar 

  • Gary SC, Hockfield S (2000) BEHAB/brevican: an extracellular matrix component associated with invasive glioma. Clin Neurosurg 47:72–82

    PubMed  CAS  Google Scholar 

  • Gary SC, Zerillo CA, Chiang VL et al (2000) cDNA cloning, chromosomal localization, and expression analysis of human BEHAB/brevican, a brain specific proteoglycan regulated during cortical development and in glioma. Gene 256:139–147

    PubMed  CAS  Google Scholar 

  • GrandPre T, Li S, Strittmatter SM (2002) Nogo-66 receptor antagonist peptide promotes axonal regeneration. Nature 417:547–551

    PubMed  CAS  Google Scholar 

  • Haas CA, Rauch U, Thon N et al (1999) Entorhinal cortex lesion in adult rats induces the expression of the neuronal chondroitin sulfate proteoglycan neurocan in reactive astrocytes. J Neurosci 19:9953–9963

    PubMed  CAS  Google Scholar 

  • Haddock G, Cross AK, Allan S et al (2007) Brevican and phosphacan expression and localization following transient middle cerebral artery occlusion in the rat. Biochem Soc Trans 35:692–694

    PubMed  CAS  Google Scholar 

  • Hagihara K, Miura R, Kosaki R et al (1999) Immunohistochemical evidence for the brevican-tenascin-R interaction: colocalization in perineuronal nets suggests a physiological role for the interaction in the adult rat brain. J Comp Neurol 410:256–264

    PubMed  CAS  Google Scholar 

  • Hamel MG, Mayer J, Gottschall PE (2005) Altered production and proteolytic processing of brevican by transforming growth factor beta in cultured astrocytes. J Neurochem 93:1533–1541

    PubMed  CAS  Google Scholar 

  • Haunsø A, Ibrahim M, Bartsch U et al (2000) Morphology of perineuronal nets in tenascin-R and parvalbumin single and double knockout mice. Brain Res 864:142–145

    PubMed  Google Scholar 

  • Held-Feindt J, Paredes EB, Blömer U et al (2006) Matrix-degrading proteases ADAMTS4 and ADAMTS5 (disintegrins and metalloproteinases with thrombospondin motifs 4 and 5) are expressed in human glioblastomas. Int J Cancer 118:55–61

    PubMed  CAS  Google Scholar 

  • Hirakawa S, Oohashi T, Su WD et al (2000) The brain link protein-1 (BRAL1): cDNA cloning, genomic structure, and characterization as a novel link protein expressed in adult brain. Biochem Biophys Res Commun 276:982–989

    PubMed  CAS  Google Scholar 

  • Hu B, Kong LL, Matthews RT, Viapiano MS (2008) The proteoglycan brevican binds to fibronectin after proteolytic cleavage and promotes glioma cell motility. J Biol Chem 283:24848–24859

    PubMed  CAS  Google Scholar 

  • Ida M, Shuo T, Hirano K et al (2006) Identification and functions of chondroitin sulfate in the milieu of neural stem cells. J Biol Chem 281:5982–5991

    PubMed  CAS  Google Scholar 

  • Inatani M, Tanihara H (2002) Proteoglycans in retina. Prog Retin Eye Res 21:429–447

    PubMed  CAS  Google Scholar 

  • Inatani M, Tanihara H, Oohira A et al (2000) Upregulated expression of neurocan, a nervous tissue specific proteoglycan, in transient retinal ischemia. Invest Ophthalmol Vis Sci 41:2748–2754

    PubMed  CAS  Google Scholar 

  • Inatani M, Honjo M, Otori Y et al (2001) Inhibitory effects of neurocan and phosphacan on neurite outgrowth from retinal ganglion cells in culture. Invest Ophthalmol Vis Sci 42:1930–1938

    PubMed  CAS  Google Scholar 

  • Jaworski DM, Kelly GM, Piepmeier JM et al (1996) BEHAB (brain enriched hyaluronan binding) is expressed in surgical samples of glioma and in intracranial grafts of invasive glioma cell lines. Cancer Res 56:2293–2298

    PubMed  CAS  Google Scholar 

  • John N, Krügel H, Frischknecht R et al (2006) Brevican-containing perineuronal nets of extracellular matrix in dissociated hippocampal primary cultures. Mol Cell Neurosci 31:774–784

    PubMed  CAS  Google Scholar 

  • Jones LL, Yamaguchi Y, Stallcup WB, Tuszynski MH (2002) NG2 is a major chondroitin sulfate proteoglycan produced after spinal cord injury and is expressed by macrophages and oligodendrocyte progenitors. J Neurosci 22:2792–2803

    PubMed  CAS  Google Scholar 

  • Jones LL, Margolis RU, Tuszynski MH (2003a) The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury. Exp Neurol 182:399–411

    PubMed  CAS  Google Scholar 

  • Jones LL, Sajed D, Tuszynski MH (2003b) Axonal regeneration through regions of chondroitin sulfate proteoglycan deposition after spinal cord injury: a balance of permissiveness and inhibition. J Neurosci 23:9276–9288

    PubMed  CAS  Google Scholar 

  • Kappler J, Stichel CC, Gleichmann M et al (1998) Developmental regulation of decorin expression in postnatal rat brain. Brain Res 793:328–332

    PubMed  CAS  Google Scholar 

  • Katoh-Semba R, Matsuda M, Watanabe E et al (1998) Two types of brain chondroitin sulfate proteoglycan: their distribution and possible functions in the rat embryo. Neurosci Res 31:273–282

    PubMed  CAS  Google Scholar 

  • Kurazono S, Okamoto M, Sakiyama J et al (2001) Expression of brain specific chondroitin sulfate proteoglycans, neurocan and phosphacan, in the developing and adult hippocampus of Ihara’s epileptic rats. Brain Res 898:36–48

    PubMed  CAS  Google Scholar 

  • Lemons ML, Sandy JD, Anderson DK, Howland DR (2001) Intact aggrecan and fragments generated by both aggrecanse and metalloproteinase-like activities are present in the developing and adult rat spinal cord and their relative abundance is altered by injury. J Neurosci 21:4772–4781

    PubMed  CAS  Google Scholar 

  • Leonardo CC, Eakin AK, Ajmo JM, Gottschall PE (2008) Versican and brevican are expressed with distinct pathology in neonatal hypoxic-ischemic injury. J Neurosci Res 86:1106–1114

    PubMed  CAS  Google Scholar 

  • Leung KM, Margolis RU, Chan SO (2004) Expression of phosphacan and neurocan during early development of mouse retinofugal pathway. Brain Res Dev Brain Res 152:1–10

    PubMed  CAS  Google Scholar 

  • Levine JM, Nishiyama A (1996) The NG2 chondroitin sulfate proteoglycan: a multifunctional proteoglycan associated with immature cells. Perspect Dev Neurobiol 3:245–259

    PubMed  CAS  Google Scholar 

  • Li H, Leung TC, Hoffman S, Balsamo J, Lilien J (2000) Coordinate regulation of cadherin and integrin function by the chondroitin sulfate proteoglycan neurocan. J Cell Biol 149:1275–1288

    PubMed  CAS  Google Scholar 

  • Li HP, Oohira A, Ogawa M et al (2005) Aberrant trajectory of thalamocortical axons associated with abnormal localization of neurocan immunoreactivity in the cerebral neocortex of reeler mutant mice. Eur J Neurosci 22:2689–2696

    PubMed  Google Scholar 

  • Lundell A, Olin AI, Mörgelin M, al-Karadaghi S, Aspberg A, Logan DT (2004) Structural basis for interactions between tenascins and lectican C-type lectin domains: evidence for a crosslinking role for tenascins. Structure 12:1495–1506

    PubMed  CAS  Google Scholar 

  • Margolis RK, Rauch U, Maurel P, Margolis RU (1996) Neurocan and phosphacan: two major nervous tissue-specific chondroitin sulfate proteoglycans. Perspect Dev Neurobiol 3:273–290

    PubMed  CAS  Google Scholar 

  • Matsui F, Watanabe E, Oohira A (1994) Immunological identification of two proteoglycan fragments derived from neurocan, a brain-specific chondroitin sulfate proteoglycan. Neurochem Int 25:425–431

    PubMed  CAS  Google Scholar 

  • Matsui F, Nishizuka M, Yasuda Y et al (1998) 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 790:45–51

    PubMed  CAS  Google Scholar 

  • Matsui F, Kawashima S, Shuo T et al (2002) Transient expression of juvenile-type neurocan by reactive astrocytes in adult rat brains injured by kainate-induced seizures as well as surgical incision. Neuroscience 112:773–781

    PubMed  CAS  Google Scholar 

  • Matsui F, Kakizawa H, Nishizuka M et al (2005) Changes in the amounts of chondroitin sulfate proteoglycans in rat brain after neonatal hypoxia-ischemia. J Neurosci Res 81:837–845

    PubMed  CAS  Google Scholar 

  • Matthews RT, Gary SC, Zerillo C et al (2000) Brain-enriched hyaluronan binding (BEHAB)/brevican cleavage in a glioma cell line is mediated by a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family member. J Biol Chem 275:22695–22703

    PubMed  CAS  Google Scholar 

  • Mayer J, Hamel MG, Gottschall PE (2005) Evidence for proteolytic cleavage of brevican by the ADAMTSs in the dentate gyrus after excitotoxic lesion of the mouse entorhinal cortex. BMC Neurosci 6:52

    PubMed  Google Scholar 

  • McKeon RJ, Jurynec MJ, Buck CR (1999) The chondroitin sulfate proteoglycans neurocan and phosphacan are expressed by reactive astrocytes in the chronic CNS glial scar. J Neurosci 19:10778–10788

    PubMed  CAS  Google Scholar 

  • Meyer-Puttlitz B, Milev P, Junker E et al (1995) Chondroitin sulfate and chondroitin/keratan sulfate proteoglycans of nervous tissue: developmental changes of neurocan and phosphacan. J Neurochem 65:2327–2337

    PubMed  CAS  Google Scholar 

  • Meyer-Puttlitz B, Junker E, Margolis RU, Margolis RK (1996) Chondroitin sulfate proteoglycans in the developing central nervous system. II. Immunocytochemical localization of neurocan and phosphacan. J Comp Neurol 366:44–54

    PubMed  CAS  Google Scholar 

  • Milev P, Maurel P, Häring M, Margolis RK, Margolis RU (1996) TAG-1/axonin-1 is a high-affinity ligand of neurocan, phosphacan/protein-tyrosine phosphatase- ζ/β, and N-CAM. J Biol Chem 271:15716–15723

    PubMed  CAS  Google Scholar 

  • Milev P, Fischer D, Häring M et al (1997) The fibrinogen-like globe of tenascin-C mediates its interactions with neurocan and phosphacan/protein-tyrosine phosphatase- ζ/β. J Biol Chem 272:15501–15509

    PubMed  CAS  Google Scholar 

  • Milev P, Chiba A, Häring M et al (1998a) High affinity binding and overlapping localization of neurocan and phosphacan/protein-tyrosine phosphatase- ζ/β with tenascin-R, amphoterin, and the heparin-binding growth-associated molecule. J Biol Chem 273:6998–7005

    PubMed  CAS  Google Scholar 

  • Milev P, Maurel P, Chiba A et al (1998b) Differential regulation of expression of hyaluronan-binding proteoglycans in developing brain: aggrecan, versican, neurocan, and brevican. Biochem Biophys Res Commun 247:207–212

    PubMed  CAS  Google Scholar 

  • Miller B, Sheppard AM, Bicknese AR, Pearlman AL (1995) Chondroitin sulfate proteoglycans in the developing cerebral cortex: the distribution of neurocan distinguishes forming afferent and efferent axonal pathways. J Comp Neurol 355:615–628

    PubMed  CAS  Google Scholar 

  • Minor K, Tang X, Kahrilas G et al (2008) Decorin promotes robust axon growth on inhibitory CS-PGs and myelin via a direct effect on neurons. Neurobiol Dis 32:88–95

    PubMed  CAS  Google Scholar 

  • Mishima N, Hoffman S (2003) Neurocan in the embryonic avian heart and vasculature. Anat Rec A Discov Mol Cell Evol Biol 272:556–562

    PubMed  Google Scholar 

  • Miura R, Aspberg A, Ethell IM et al (1999) The proteoglycan lectin domain binds sulfated cell surface glycolipids and promotes cell adhesion. J Biol Chem 274:11431–11438

    PubMed  CAS  Google Scholar 

  • Miura R, Ethell IM, Yamaguchi Y (2001) Carbohydrate-protein interactions between HNK-1-reactive sulfoglucuronyl glycolipids and the proteoglycan lectin domain mediate neuronal cell adhesion and neurite outgrowth. J Neurochem 76:413–432

    PubMed  CAS  Google Scholar 

  • Mizuno H, Warita H, Aoki M, Itoyama Y (2008) Accumulation of chondroitin sulfate proteoglycans in the microenvironment of spinal motor neurons in amyotrophic lateral sclerosis transgenic rats. J Neurosci Res 86:2512–2523

    PubMed  CAS  Google Scholar 

  • Monnier PP, Sierra A, Schwab JM et al (2003) The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar. Mol Cell Neurosci 22:319–332

    PubMed  CAS  Google Scholar 

  • Morgenstern DA, Asher RA, Fawcett JW (2002) Chondroitin sulphate proteoglycans in the CNS injury response. Prog Brain Res 137:313–332

    PubMed  CAS  Google Scholar 

  • Nakada M, Miyamori H, Kita D et al (2005) Human glioblastomas overexpress ADAMTS-5 that degrades brevican. Acta Neuropathol 110:239–246

    PubMed  CAS  Google Scholar 

  • Neumann S, Woolf CJ (1999) Regeneration of dorsal column fibers into and beyond the lesion site following adult spinal cord injury. Neuron 23:83–91

    PubMed  CAS  Google Scholar 

  • Neumann S, Skinner K, Basbaum AI (2005) Sustaining intrinsic growth capacity of adult neurons promotes spinal cord regeneration. Proc Natl Acad Sci USA 102:16848–16852

    PubMed  CAS  Google Scholar 

  • Nutt CL, Zerillo CA, Kelly GM, Hockfield S (2001) Brain enriched hyaluronan binding (BEHAB)/brevican increases aggressiveness of CNS-1 gliomas in Lewis rats. Cancer Res 61:7056–7059

    PubMed  CAS  Google Scholar 

  • Ogawa T, Hagihara K, Suzuki M et al (2001) Brevican in the developing hippocampal fimbria: differential expression in myelinating oligodendrocytes and adult astrocytes suggests a dual role for brevican in central nervous system fiber tract development. J Comp Neurol 432:285–295

    PubMed  CAS  Google Scholar 

  • Okamoto M, Sakiyama J, Kurazono S et al (2001) Developmentally regulated expression of brain-specific chondroitin sulfate proteoglycans, neurocan and phosphacan, in the postnatal rat hippocampus. Cell Tissue Res 306:217–229

    PubMed  CAS  Google Scholar 

  • Oleszewski M, Gutwein P, von der Lieth W et al (2000) Characterization of the L1-neurocan-binding site. Implications for L1-L1 homophilic binding. J Biol Chem 275:34478–34485

    PubMed  CAS  Google Scholar 

  • Oohashi T, Hirakawa S, Bekku Y et al (2002) Bral1, a brain-specific link protein, colocalizing with the versican V2 isoform at the nodes of Ranvier in developing and adult mouse central nervous systems. Mol Cell Neurosci 19:43–57

    PubMed  CAS  Google Scholar 

  • Popp S, Maurel P, Andersen JS, Margolis RU (2004) Developmental changes of aggrecan, versican and neurocan in the retina and optic nerve. Exp Eye Res 79:351–356

    PubMed  CAS  Google Scholar 

  • Porter S, Clark IM, Kevorkian L, Edwards DR (2005) The ADAMTS metalloproteinases. Biochem J 386:15–27

    PubMed  CAS  Google Scholar 

  • Prange CK, Pennacchio LA, Lieuallen K et al (1998) Characterization of the human neurocan gene, CS-PG3. Gene 221:199–205

    PubMed  CAS  Google Scholar 

  • Qi ML, Wakabayashi Y, Enomoto M, Shinomiya K (2003) Changes in neurocan expression in the distal spinal cord stump following complete cord transection: a comparison between infant and adult rats. Neurosci Res 45:181–188

    PubMed  CAS  Google Scholar 

  • Quaglia X, Beggah AT, Seidenbecher C, Zurn AD (2008) Delayed priming promotes CNS regeneration post-rhizotomy in neurocan and brevican-deficient mice. Brain 131:240–249

    PubMed  CAS  Google Scholar 

  • Rauch U (2004) Extracellular matrix components associated with remodeling processes in brain. Cell Mol Life Sci 61:2031–2045

    PubMed  CAS  Google Scholar 

  • Rauch U, Karthikeyan L, Maurel P et al (1992) Cloning and primary structure of neurocan, a developmentally regulated, aggregating chondroitin sulfate proteoglycan of brain. J Biol Chem 267:19536–19547

    PubMed  CAS  Google Scholar 

  • Rauch U, Grimpe B, Kulbe G et al (1995) Structure and chromosomal localization of the mouse neurocan gene. Genomics 28:405–410

    PubMed  CAS  Google Scholar 

  • Rauch U, Clement A, Retzler C, Fröhlich L et al (1997a) Mapping of a defined neurocan binding site to distinct domains of tenascin-C. J Biol Chem 272:26905–26912

    PubMed  CAS  Google Scholar 

  • Rauch U, Meyer H, Brakebusch C et al (1997b) Sequence and chromosomal localization of the mouse brevican gene. Genomics 44:15–21

    PubMed  CAS  Google Scholar 

  • Rauch U, Feng K, Zhou XH (2001) Neurocan: a brain chondroitin sulfate proteoglycan. Cell Mol Life Sci 58:1842–1856

    PubMed  CAS  Google Scholar 

  • Rauch U, Zhou XH, Roos G (2005) Extracellular matrix alterations in brains lacking four of its components. Biochem Biophys Res Commun 328:608–617

    PubMed  CAS  Google Scholar 

  • Retzler C, Göhring W, Rauch U (1996b) Analysis of neurocan structures interacting with the neural cell adhesion molecule N-CAM. J Biol Chem 271:27304–27310

    PubMed  CAS  Google Scholar 

  • Retzler C, Wiedemann H, Kulbe G, Rauch U (1996a) Structural and electron microscopic analysis of neurocan and recombinant neurocan fragments. J Biol Chem 271:17107–17113

    PubMed  CAS  Google Scholar 

  • Richardson PM, Issa VM (1984) Peripheral injury enhances central regeneration of primary sensory neurones. Nature 309:791–793

    PubMed  CAS  Google Scholar 

  • Sango K, Oohira A, Ajiki K et al (2003) Phosphacan and neurocan are repulsive substrata for adhesion and neurite extension of adult rat dorsal root ganglion neurons in vitro. Exp Neurol 182:1–11

    PubMed  CAS  Google Scholar 

  • Schäfer R, Dehn D, Burbach GJ, Deller T (2008) Differential regulation of chondroitin sulfate proteoglycan mRNAs in the denervated rat fascia dentata after unilateral entorhinal cortex lesion. Neurosci Lett 439:61–65

    PubMed  Google Scholar 

  • Schmalfeldt M, Dours-Zimmermann MT, Winterhalter KH, Zimmermann DR (1998) Versican V2 is a major extracellular matrix component of the mature bovine brain. J Biol Chem 273:15758–15764

    PubMed  CAS  Google Scholar 

  • Schnell L, Schwab ME (1990) Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors. Nature 343:269–272

    PubMed  CAS  Google Scholar 

  • Schnepp A, Lindgren PK, Hülsmann H et al (2005) Mouse Testican-2: Eexpression, glycosylation, and effects on neurite outgrowth. J Biol Chem 280(12):11274–11280

    PubMed  CAS  Google Scholar 

  • Schwartz NB, Domowicz M (2004) Proteoglycans in brain development. Glycoconj J 21:329–341

    PubMed  CAS  Google Scholar 

  • Seidenbecher CI, Richter K, Rauch U et al (1995) Brevican, a chondroitin sulfate proteoglycan of rat brain, occurs as secreted and cell surface glycosylphosphatidylinositol-anchored isoforms. J Biol Chem 270:27206–27212

    PubMed  CAS  Google Scholar 

  • Seidenbecher CI, Gundelfinger ED, Böckers TM et al (1998) Transcripts for secreted and GPI-anchored brevican are differentially distributed in rat brain. Eur J Neurosci 10:1621–1632

    PubMed  CAS  Google Scholar 

  • Seidenbecher CI, Smalla KH, Fischer N et al (2002) Brevican isoforms associate with neural membranes. J Neurochem 83:738–746

    PubMed  CAS  Google Scholar 

  • Seyfried NT, McVey GF, Almond A et al (2005) Expression and purification of functionally active hyaluronan-binding domains from human cartilage link protein, aggrecan and versican: formation of ternary complexes with defined hyaluronan oligosaccharides. J Biol Chem 280:5435–5448

    PubMed  CAS  Google Scholar 

  • Shen LH, Li Y, Gao Q et al (2008) Down-regulation of neurocan expression in reactive astrocytes promotes axonal regeneration and facilitates the neurorestorative effects of bone marrow stromal cells in the ischemic rat brain. Glia 56:1747–1754

    PubMed  Google Scholar 

  • Shuo T, Aono S, Matsui F et al (2004) Developmental changes in the biochemical and immunological characters of the carbohydrate moiety of neuroglycan C, a brain-specific chondroitin sulfate proteoglycan. Glycoconj J 20:267–278

    PubMed  CAS  Google Scholar 

  • Silver J, Miller JH (2004) Regeneration beyond the glial scar. Nat Rev Neurosci 5:146–156

    PubMed  CAS  Google Scholar 

  • Sivasankaran R, Pei J, Wang KC et al (2004) PKC mediates inhibitory effects of myelin and chondroitin sulfate proteoglycans on axonal regeneration. Nat Neurosci 7:261–268

    PubMed  CAS  Google Scholar 

  • Smith GM, Strunz C (2005) Growth factor and cytokine regulation of chondroitin sulfate proteoglycans by astrocytes. Glia 52:209–218

    PubMed  Google Scholar 

  • Sobel RA, Ahmed AS (2001) White matter extracellular matrix chondroitin sulfate/dermatan sulfate proteoglycans in multiple sclerosis. J Neuropathol Exp Neurol 60:1198–1207

    PubMed  CAS  Google Scholar 

  • Spicer AP, Joo A, Bowling RA Jr (2003) 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 278:21083–21091

    PubMed  CAS  Google Scholar 

  • Tang X, Davies JE, Davies SJ (2003) Changes in distribution, cell associations, and protein expression levels of NG2, neurocan, phosphacan, brevican, versican V2, and tenascin-C during acute to chronic maturation of spinal cord scar tissue. J Neurosci Res 71:427–444

    PubMed  CAS  Google Scholar 

  • Thon N, Haas CA, Rauch U et al (2000) The chondroitin sulphate proteoglycan brevican is upregulated by astrocytes after entorhinal cortex lesions in adult rats. Eur J Neurosci 12:2547–2558

    PubMed  CAS  Google Scholar 

  • Toba Y, Horie M, Sango K et al (2002) Expression and immunohisto-chemical localization of heparan sulphate proteoglycan N-syndecan in the migratory pathway from the rat olfactory placode. Eur J Neurosci 15:1461–1473

    PubMed  Google Scholar 

  • Ughrin YM, Chen ZJ, Levine JM (2003) Multiple regions of the NG2 proteoglycan inhibit neurite growth and induce growth cone collapse. J Neurosci 23:175–186

    PubMed  CAS  Google Scholar 

  • Viapiano MS, Hockfield S, Matthews RT (2008) BEHAB/brevican requires ADAMTS-mediated proteolytic cleavage to promote glioma invasion. J Neurooncol 88:261–272

    PubMed  CAS  Google Scholar 

  • Vitellaro-Zuccarello L, Bosisio P, Mazzetti S et al (2007) Differential expression of several molecules of the extracellular matrix in functionally and developmentally distinct regions of rat spinal cord. Cell Tissue Res 327:433–447

    PubMed  CAS  Google Scholar 

  • Wang W, Dow KE (1997) Differential regulation of neuronal proteoglycans by activation of excitatory amino acid receptors. Neuroreport 8:659–663

    PubMed  CAS  Google Scholar 

  • Watanabe E, Aono S, Matsui F et al (1995) Distribution of a brain-specific proteoglycan, neurocan, and the corresponding mRNA during the formation of barrels in the rat somatosensory cortex. Eur J Neurosci 7:547–554

    PubMed  CAS  Google Scholar 

  • Wilson MT, Snow DM (2000) Chondroitin sulfate proteoglycan expression pattern in hippocampal development: potential regulation of axon tract formation. J Comp Neurol 424:532–546

    PubMed  CAS  Google Scholar 

  • Wu Y, Sheng W, Chen L et al (2004) Versican V1 isoform induces neuronal differentiation and promotes neurite outgrowth. Mol Biol Cell 15:2093–2104

    PubMed  CAS  Google Scholar 

  • Xiao ZC, Bartsch U, Margolis RK et al (1997) Isolation of a tenascin-R binding protein from mouse brain membranes. A phosphacan-related chondroitin sulfate proteoglycan. J Biol Chem 272:32092–32101

    PubMed  CAS  Google Scholar 

  • Yamada H, Watanabe K, Shimonaka M, Yamaguchi Y (1994) Molecular cloning of brevican, a novel brain proteoglycan of the aggrecan/versican family. J Biol Chem 269:10119–10126

    PubMed  CAS  Google Scholar 

  • Yamada H, Watanabe K, Shimonaka M et al (1995) cDNA cloning and the identification of an aggrecanase-like cleavage site in rat brevican. Biochem Biophys Res Commun 216:957–963

    PubMed  CAS  Google Scholar 

  • Yamada H, Fredette B, Shitara K et al (1997) The brain chondroitin sulfate proteoglycan brevican associates with astrocytes ensheathing cerebellar glomeruli and inhibits neurite outgrowth from granule neurons. J Neurosci 17:7784–7795

    PubMed  CAS  Google Scholar 

  • Zacharias U, Rauch U (2006) Competition and cooperation between tenascin-R, lecticans and contactin 1 regulate neurite growth and morphology. J Cell Sci 119:3456–3466

    PubMed  CAS  Google Scholar 

  • Zanin MK, Bundy J, Ernst H et al (1999) Distinct spatial and temporal distributions of aggrecan and versican in the embryonic chick heart. Anat Rec 256:366–380

    PubMed  CAS  Google Scholar 

  • Zhang H, Kelly G, Zerillo C et al (1998) Expression of a cleaved brain-specific extracellular matrix protein mediates glioma cell invasion In vivo. J Neurosci 18:2370–2376

    PubMed  CAS  Google Scholar 

  • Zhang Y, Rauch U, Perez MT (2003) Accumulation of neurocan, a brain chondroitin sulfate proteoglycan, in association with the retinal vasculature in RCS rats. Invest Ophthalmol Vis Sci 44:1252–1261

    PubMed  Google Scholar 

  • Zhou XH, Brakebusch C, Matthies H et al (2001) Neurocan is dispensable for brain development. Mol Cell Biol 21:5970–5978

    PubMed  CAS  Google Scholar 

  • Zimmermann DR, Dours-Zimmermann MT (2008) Extracellular matrix of the central nervous system: from neglect to challenge. Histochem Cell Biol 130:635–653

    PubMed  CAS  Google Scholar 

  • Zurn AD, Bandtlow CE (2006) Regeneration failure in the CNS: cellular and molecular mechanisms. Adv Exp Med Biol 557:54–76

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Wien

About this chapter

Cite this chapter

Gupta, G.S. (2012). Proteoglycans of the Central Nervous System. In: Animal Lectins: Form, Function and Clinical Applications. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1065-2_38

Download citation

Publish with us

Policies and ethics