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BioMed Research International
Volume 2014, Article ID 642798, 11 pages
http://dx.doi.org/10.1155/2014/642798
Review Article

Chondroitin Sulfate Proteoglycans: Structure-Function Relationship with Implication in Neural Development and Brain Disorders

1Anatomy, Animal Physiology and Biophysics Department, Faculty of Biology, University of Bucharest, 91-95th Independentei Street, 050095 Bucharest, Romania
2Norgenotech AS, Totenvegen 2049, 2848 Skreia, Norway
3Automatic Control and Systems Engineering Department, Faculty of Automatic Control and Computers, “Politehnica” University of Bucharest, 313th Independentei Street, 060042 Bucharest, Romania

Received 28 February 2014; Revised 28 April 2014; Accepted 28 April 2014; Published 14 May 2014

Academic Editor: Sun-On Chan

Copyright © 2014 Speranta Avram et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. Geissler, C. Gottschling, A. Aguado et al., “Primary hippocampal neurons, which lack four crucial extracellular matrix molecules, display abnormalities of synaptic structure and function and severe deficits in perineuronal net formation,” The Journal of Neuroscience, vol. 33, no. 18, pp. 7742–7755, 2013. View at Google Scholar
  2. G. Perea, M. Navarrete, and A. Araque, “Tripartite synapses: astrocytes process and control synaptic information,” Trends in Neurosciences, vol. 32, no. 8, pp. 421–431, 2009. View at Publisher · View at Google Scholar · View at Scopus
  3. M. A. Di Castro, J. Chuquet, N. Liaudet et al., “Local Ca2+ detection and modulation of synaptic release by astrocytes,” Nature Neuroscience, vol. 14, no. 10, pp. 1276–1284, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. Y. Bekku and T. Oohashi, “Neurocan contributes to the molecular heterogeneity of the perinodal ECM,” Archives of Histology and Cytology, vol. 73, no. 2, pp. 95–102, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. S. Wiese, M. Karus, and A. Faissner, “Astrocytes as a source for extracellular matrix molecules and cytokines,” Frontiers in Pharmacology, vol. 3, p. 120, 2012. View at Google Scholar
  6. C. E. Bandtlow and D. R. Zimmermann, “Proteoglycans in the developing brain: new conceptual insights for old proteins,” Physiological Reviews, vol. 80, no. 4, pp. 1267–1290, 2000. View at Google Scholar · View at Scopus
  7. J. H. Yi, Y. Katagiri, B. Susarla, D. Figge, A. J. Symes, and H. M. Geller, “Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice,” Journal of Comparative Neurology, vol. 520, no. 15, pp. 3295–3313, 2012. View at Google Scholar
  8. L. L. Jones, R. U. Margolis, and M. H. Tuszynski, “The chondroitin sulfate proteoglycans neurocan, brevican, phosphacan, and versican are differentially regulated following spinal cord injury,” Experimental Neurology, vol. 182, no. 2, pp. 399–411, 2003. View at Publisher · View at Google Scholar · View at Scopus
  9. P. P. Monnier, A. Sierra, J. M. Schwab, S. Henke-Fahle, and B. K. Mueller, “The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar,” Molecular and Cellular Neuroscience, vol. 22, no. 3, pp. 319–330, 2003. View at Publisher · View at Google Scholar · View at Scopus
  10. B. Meyer-Puttlitz, P. Milev, E. Junker, I. Zimmer, R. U. Margolis, and R. K. Margolis, “Chondroitin sulfate and chondroitin/keratan sulfate proteoglycans of nervous tissue: developmental changes of neurocan and phosphacan,” Journal of Neurochemistry, vol. 65, no. 5, pp. 2327–2337, 1995. View at Google Scholar · View at Scopus
  11. S. Dutt, E. Cassoly, M. T. Dours-Zimmermann, M. Matasci, E. T. Stoeckli, and D. R. Zimmermann, “Versican V0 and V1 direct the growth of peripheral axons in the developing chick hindlimb,” Journal of Neuroscience, vol. 31, no. 14, pp. 5262–5270, 2011. View at Publisher · View at Google Scholar · View at Scopus
  12. T. L. Laabs, H. Wang, Y. Katagiri, T. McCann, J. W. Fawcett, and H. M. Geller, “Inhibiting glycosaminoglycan chain polymerization decreases the inhibitory activity of astrocyte-derived chondroitin sulfate proteoglycans,” Journal of Neuroscience, vol. 27, no. 52, pp. 14494–14501, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. N. Bukhari, L. Torres, J. K. Robinson, and S. E. Tsirka, “Axonal regrowth after spinal cord injury via chondroitinase and the tissue plasminogen activator (tPA)/plasmin system,” Journal of Neuroscience, vol. 31, no. 42, pp. 14931–14943, 2011. View at Publisher · View at Google Scholar · View at Scopus
  14. D. Carulli, T. Pizzorusso, J. C. F. Kwok et al., “Animals lacking link protein have attenuated perineuronal nets and persistent plasticity,” Brain, vol. 133, no. 8, pp. 2331–2347, 2010. View at Publisher · View at Google Scholar · View at Scopus
  15. D. Wang, R. M. Ichiyama, R. Zhao, M. R. Andrews, and J. W. Fawcett, “Chondroitinase combined with rehabilitation promotes recovery of forelimb function in rats with chronic spinal cord injury,” Journal of Neuroscience, vol. 31, no. 25, pp. 9332–9344, 2011. View at Publisher · View at Google Scholar · View at Scopus
  16. H. J. Lee, S. Bian, I. Jakovcevski, B. Wu, A. Irintchev, and M. Schachner, “Delayed applications of L1 and chondroitinase ABC promote recovery after spinal cord injury,” Journal of Neurotrauma, vol. 29, no. 10, pp. 1850–1863, 2012. View at Google Scholar
  17. T. W. Mühleisen, M. Mattheisen, J. Strohmaier et al., “Association between schizophrenia and common variation in neurocan (NCAN), a genetic risk factor for bipolar disorder,” Schizophrenia Research, vol. 138, no. 1, pp. 69–73, 2012. View at Google Scholar
  18. S. Cichon, T. W. Mühleisen, F. A. Degenhardt et al., “Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder,” American Journal of Human Genetics, vol. 88, no. 3, pp. 372–381, 2011. View at Google Scholar
  19. L. Oruc, L. Kapur-Pojskic, J. Ramic, N. Pojskic, and K. Bajrovic, “Assessment of relatedness between neurocan gene as bipolar disorder susceptibility locus and schizophrenia,” Bosnian Journal of Basic Medical Sciences, vol. 12, no. 4, pp. 245–248, 2012. View at Google Scholar
  20. K. Iseki, S. Hagino, T. Nikaido et al., “Gliosis-specific transcription factor OASIS coincides with proteoglycan core protein genes in the glial scar and inhibits neurite outgrowth,” BioMed Research, vol. 33, no. 6, pp. 345–353, 2012. View at Google Scholar
  21. H. Kitagawa, T. Uyama, and K. Sugahara, “Molecular cloning and expression of a human chondroitin synthase,” The Journal of Biological Chemistry, vol. 276, no. 42, pp. 38721–38726, 2001. View at Publisher · View at Google Scholar · View at Scopus
  22. H. Kitagawa, T. Izumikawa, T. Uyama, and K. Sugahara, “Molecular cloning of a chondroitin polymerizing factor that cooperates with chondroitin synthase for chondroitin polymerization,” The Journal of Biological Chemistry, vol. 278, no. 26, pp. 23666–23671, 2003. View at Publisher · View at Google Scholar · View at Scopus
  23. T. Izumikawa, T. Koike, S. Shiozawa, K. Sugahara, J.-I. Tamura, and H. Kitagawa, “Identification of chondroitin sulfate glucuronyltransferase as chondroitin synthase-3 involved in chondroitin polymerization: chondroitin polymerization is achieved by multiple enzyme complexes consisting of chondroitin synthase family members,” The Journal of Biological Chemistry, vol. 283, no. 17, pp. 11396–11406, 2008. View at Publisher · View at Google Scholar · View at Scopus
  24. T. Izumikawa, T. Uyama, Y. Okuura, K. Sugahara, and H. Kitagawa, “Involvement of chondroitin sulfate synthase-3 (chondroitin synthase-2) in chondroitin polymerization through its interaction with chondroitin synthase-1 or chondroitin-polymerizing factor,” Biochemical Journal, vol. 403, no. 3, pp. 545–552, 2007. View at Publisher · View at Google Scholar · View at Scopus
  25. T. Mikami and H. Kitagawa, “Biosynthesis and function of chondroitin sulfate,” Biochim Biophys Acta, 1830, no. 10, pp. 4719–4733, 2013. View at Google Scholar
  26. A. Hurtado, H. Podinin, M. Oudega, and B. Grimpe, “Deoxyribozyme-mediated knockdown of xylosyltransferase-1 mRNA promotes axon growth in the adult rat spinal cord,” Brain, vol. 131, no. 10, pp. 2596–2605, 2008. View at Publisher · View at Google Scholar · View at Scopus
  27. R. C. Cua, L. W. Lau, M. B. Keough, R. Midha, S. S. Apte, and V. W. Yong, “Overcoming neurite-inhibitory chondroitin sulfate proteoglycans in the astrocyte matrix,” Glia, vol. 61, no. 6, pp. 972–984, 2013. View at Google Scholar
  28. C. K. Prange, L. A. Pennacchio, K. Lieuallen, W. Fan, and G. G. Lennon, “Characterization of the human neurocan gene, CSPG3,” Gene, vol. 221, no. 2, pp. 199–205, 1998. View at Publisher · View at Google Scholar · View at Scopus
  29. X.-H. Zhou, C. Brakebusch, H. Matthies et al., “Neurocan is dispensable for brain development,” Molecular and Cellular Biology, vol. 21, no. 17, pp. 5970–5978, 2001. View at Publisher · View at Google Scholar · View at Scopus
  30. U. Rauch, A. Clement, C. Retzler et al., “Mapping of a defined neurocan binding site to distinct domains of tenascin-C,” The Journal of Biological Chemistry, vol. 272, no. 43, pp. 26905–26912, 1997. View at Google Scholar
  31. U. Rauch, K. Feng, and X.-H. Zhou, “Neurocan: a brain chondroitin sulfate proteoglycan,” Cellular and Molecular Life Sciences, vol. 58, no. 12-13, pp. 1842–1856, 2001. View at Google Scholar · View at Scopus
  32. C. Retzler, W. Gohring, and U. Rauch, “Analysis of neurocan structures interacting with the neural cell adhesion molecule N-CAM,” The Journal of Biological Chemistry, vol. 271, no. 44, pp. 27304–27310, 1996. View at Google Scholar
  33. L. Y. Geer, A. Marchler-Bauer, R. C. Geer et al., “The NCBI BioSystems database,” Nucleic Acids Research, vol. 38, no. 1, pp. D492–D496, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. M. Magrane and U. Consortium, “UniProt Knowledgebase: a hub of integrated protein data,” Database, vol. 2011, p. bar009, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. R. V. Iozzo and A. D. Murdoch, “Proteoglycans of the extracellular environment: clues from the gene and protein side offer novel perspectives in molecular diversity and function,” The FASEB Journal, vol. 10, no. 5, pp. 598–614, 1996. View at Google Scholar
  36. N. T. Seyfried, G. F. McVey, A. Almond, D. J. Mahoney, J. Dudhia, and A. J. Day, “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,” The Journal of Biological Chemistry, vol. 280, no. 7, pp. 5435–5448, 2005. View at Publisher · View at Google Scholar · View at Scopus
  37. P. Teriete, S. Banerji, M. Noble et al., “Structure of the regulatory hyaluronan binding domain in the inflammatory leukocyte homing receptor CD44,” Molecular Cell, vol. 13, no. 4, pp. 483–496, 2004. View at Publisher · View at Google Scholar · View at Scopus
  38. E. M. Wood-Charlson and V. M. Weis, “The diversity of C-type lectins in the genome of a basal metazoan, Nematostella vectensis,” Developmental and Comparative Immunology, vol. 33, no. 8, pp. 881–889, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. Y. van Kooyk, “C-type lectins on dendritic cells: key modulators for the induction of immune responses,” Biochemical Society Transactions, vol. 36, no. 6, pp. 1478–1481, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. M. Cardone, K. N. Ikeda, B. Varano et al., “Opposite regulatory effects of IFN-beta and IL-3 on C-type lectin receptors, antigen uptake, and phagocytosis in human macrophages,” Journal of Leukocyte Biology, vol. 95, no. 1, pp. 161–168, 2014. View at Google Scholar
  41. K. Gijzen, A. Cambi, R. Torensma, and C. G. Figdor, “C-type lectins on dendritic cells and their interaction with pathogen-derived and endogenous glycoconjugates,” Current Protein and Peptide Science, vol. 7, no. 4, pp. 283–294, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Pyka, C. Wetzel, A. Aguado, M. Geissler, H. Hatt, and A. Faissner, “Chondroitin sulfate proteoglycans regulate astrocyte-dependent synaptogenesis and modulate synaptic activity in primary embryonic hippocampal neurons,” European Journal of Neuroscience, vol. 33, no. 12, pp. 2187–2202, 2011. View at Publisher · View at Google Scholar · View at Scopus
  43. L. Gasimli, H. E. Stansfield, A. V. Nairn et al., “Structural remodeling of proteoglycans upon retinoic acid-induced differentiation of NCCIT cells,” Glycoconjugate Journal, vol. 30, no. 5, pp. 497–510, 2013. View at Google Scholar
  44. S. Hoffman, B. C. Sorkin, P. C. White et al., “Chemical characterization of a neural cell adhesion molecule purified from embryonic brain membranes,” The Journal of Biological Chemistry, vol. 257, no. 13, pp. 7720–7729, 1982. View at Google Scholar · View at Scopus
  45. Y. Rao, X.-F. Wu, J. Gariepy, U. Rutishauser, and C.-H. Siu, “Identification of a peptide sequence involved in homophilic binding in the neural cell adhesion molecule NCAM,” Journal of Cell Biology, vol. 118, no. 4, pp. 937–949, 1992. View at Google Scholar · View at Scopus
  46. C. Kasper, H. Rasmussen, J. S. Kastrup et al., “Structural basis of cell-cell adhesion by NCAM,” Nature Structural Biology, vol. 7, no. 5, pp. 389–393, 2000. View at Publisher · View at Google Scholar · View at Scopus
  47. O. Nybroe, N. Moran, and E. Bock, “Equilibrium binding analysis of neural cell adhesion molecule binding to heparin,” Journal of Neurochemistry, vol. 52, no. 6, pp. 1947–1949, 1989. View at Google Scholar · View at Scopus
  48. R. Horstkorte, M. Schachner, J. P. Magyar, T. Vorherr, and B. Schmitz, “The fourth immunoglobulin-like domain of NCAM contains a carbohydrate recognition domain for oligomannosidic glycans implicated in association with L1 and neurite outgrowth,” Journal of Cell Biology, vol. 121, no. 6, pp. 1409–1422, 1993. View at Google Scholar · View at Scopus
  49. V. Soroka, K. Kolkova, J. S. Kastrup et al., “Structure and interactions of NCAM Ig1-2-3 suggest a novel zipper mechanism for homophilic adhesion,” Structure, vol. 11, no. 10, pp. 1291–1301, 2003. View at Publisher · View at Google Scholar · View at Scopus
  50. N. Kulahin, O. Kristensen, K. K. Rasmussen et al., “Structural model and trans-interaction of the entire ectodomain of the olfactory cell adhesion molecule,” Structure, vol. 19, no. 2, pp. 203–211, 2011. View at Publisher · View at Google Scholar · View at Scopus
  51. F. Carafoli, J. L. Saffell, and E. Hohenester, “Structure of the tandem fibronectin type 3 domains of neural cell adhesion molecule,” Journal of Molecular Biology, vol. 377, no. 2, pp. 524–534, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. The PyMOL Molecular Graphics System, Version 1.5.0.4, Schrödinger, LLC..
  53. N. B. Schwartz and M. Domowicz, “Proteoglycans in brain development,” Glycoconjugate Journal, vol. 21, no. 6, pp. 329–341, 2004. View at Publisher · View at Google Scholar · View at Scopus
  54. S. Popp, P. Maurel, J. S. Andersen, and R. U. Margolis, “Developmental changes of aggrecan, versican and neurocan in the retina and optic nerve,” Experimental Eye Research, vol. 79, no. 3, pp. 351–356, 2004. View at Publisher · View at Google Scholar · View at Scopus
  55. M. Morawski, G. Brückner, T. Arendt, and R. T. Matthews, “Aggrecan: beyond cartilage and into the brain,” International Journal of Biochemistry and Cell Biology, vol. 44, no. 5, pp. 690–693, 2012. View at Publisher · View at Google Scholar · View at Scopus
  56. A. Aspberg, “The different roles of aggrecan interaction domains,” Journal of Histochemistry & Cytochemistry, vol. 60, no. 12, pp. 987–996, 2012. View at Google Scholar
  57. A. D. Theocharis, S. S. Skandalis, G. N. Tzanakakis, and N. K. Karamanos, “Proteoglycans in health and disease: novel roles for proteoglycans in malignancy and their pharmacological targeting,” FEBS Journal, vol. 277, no. 19, pp. 3904–3923, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. H. Wiedemann, M. Paulsson, and R. Timpl, “Domain structure of cartilage proteoglycans revealed by rotary shadowing of intact and fragmented molecules,” Biochemical Journal, vol. 224, no. 1, pp. 331–333, 1984. View at Google Scholar · View at Scopus
  59. M. Paulsson, M. Mörgelin, H. Wiedemann et al., “Extended and globular protein domains in cartilage proteoglycans,” Biochemical Journal, vol. 245, no. 3, pp. 763–772, 1987. View at Google Scholar · View at Scopus
  60. H. Watanabe, S. C. Cheung, N. Itano, K. Kimata, and Y. Yamada, “Identification of hyaluronan-binding domains of aggrecan,” The Journal of Biological Chemistry, vol. 272, no. 44, pp. 28057–28065, 1997. View at Google Scholar
  61. H. Yamada, K. Watanabe, M. Shimonaka, and Y. Yamaguchi, “Molecular cloning of brevican, a novel brain proteoglycan of the aggrecan/versican family,” The Journal of Biological Chemistry, vol. 269, no. 13, pp. 10119–10126, 1994. View at Google Scholar · View at Scopus
  62. S. Saleque, N. Ruiz, and K. Drickamer, “Expression and characterization of a carbohydrate-binding fragment of rat aggrecan,” Glycobiology, vol. 3, no. 2, pp. 185–190, 1993. View at Google Scholar · View at Scopus
  63. R. Miura, A. Aspberg, I. M. Ethell et al., “The proteoglycan lectin domain binds sulfated cell surface glycolipids and promotes cell adhesion,” The Journal of Biological Chemistry, vol. 274, no. 16, pp. 11431–11438, 1999. View at Publisher · View at Google Scholar · View at Scopus
  64. A. D. Theocharis, “Versican in health and disease,” Connective Tissue Research, vol. 49, no. 3-4, pp. 230–234, 2008. View at Publisher · View at Google Scholar · View at Scopus
  65. K. Matsumoto, M. Shionyu, M. Go et al., “Distinct interaction of versican/PG-M with hyaluronan and link protein,” The Journal of Biological Chemistry, vol. 278, no. 42, pp. 41205–41212, 2003. View at Publisher · View at Google Scholar · View at Scopus
  66. A. J. M. Yee, M. Akens, B. L. Yang et al., “The effect of versican G3 domain on local breast cancer invasiveness and bony metastasis,” Breast Cancer Research, vol. 9, no. 4, article R42, 2007. View at Publisher · View at Google Scholar · View at Scopus
  67. J. R. Siebert and D. J. Osterhout, “The inhibitory effects of chondroitin sulfate proteoglycans on oligodendrocytes,” Journal of Neurochemistry, vol. 119, no. 1, pp. 176–188, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. C. Jager, D. Lendvai, G. Seeger et al., “Perineuronal and perisynaptic extracellular matrix in the human spinal cord,” Neuroscience, vol. 238, pp. 168–184, 2013. View at Google Scholar
  69. R. Tauchi, S. Imagama, T. Natori et al., “The endogenous proteoglycan-degrading enzyme ADAMTS-4 promotes functional recovery after spinal cord injury,” Journal of Neuroinflammation, vol. 9, article 53, 2012. View at Publisher · View at Google Scholar · View at Scopus
  70. C. C. Schultz, T. W. Mühleisen, I. Nenadic et al., “Common variation in NCAN, a risk factor for bipolar disorder and schizophrenia, influences local cortical folding in schizophrenia,” Psychological Medicine, vol. 44, no. 4, pp. 811–820, 2014. View at Google Scholar
  71. X. Miro, S. Meier, M. L. Dreisow et al., “Studies in humans and mice implicate neurocan in the etiology of mania,” American Journal of Psychiatry, vol. 169, no. 9, pp. 982–990, 2012. View at Google Scholar
  72. B. G. Schimmelmann, A. Hinney, A. Scherag et al., “Bipolar disorder risk alleles in children with ADHD,” Journal of Neural Transmission, vol. 120, no. 11, pp. 1611–1617, 2013. View at Google Scholar
  73. N. Craddock and P. Sklar, “Genetics of bipolar disorder,” The Lancet, vol. 381, no. 9878, pp. 1654–1662, 2013. View at Google Scholar
  74. K. W. Lee, P. S. Woon, Y. Y. Teo, and K. Sim, “Genome wide association studies (GWAS) and copy number variation (CNV) studies of the major psychoses: what have we learnt?” Neuroscience and Biobehavioral Reviews, vol. 36, no. 1, pp. 556–571, 2012. View at Publisher · View at Google Scholar · View at Scopus
  75. J. X. Van Snellenberg and T. De Candia, “Meta-analytic evidence for familial coaggregation of schizophrenia and bipolar disorder,” Archives of General Psychiatry, vol. 66, no. 7, pp. 748–755, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. “Genome-wide association study identifies five new schizophrenia loci,” Nature Genetics, vol. 43, no. 10, pp. 969–976, 2011.
  77. S. Avram, D. Duda-Seiman, F. Borcan, and P. Wolschann, “QSAR-CoMSIA applied to antipsychotic drugs with their dopamine D2 and serotonine 5HT2A membrane receptors,” Journal of the Serbian Chemical Society, vol. 76, no. 2, pp. 263–281, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. A. Lundell, A. I. Olin, M. Mörgelin, S. Al-Karadaghi, A. Aspberg, and D. T. Logan, “Structural basis for interactions between tenascins and lectican C-type lectin domains: evidence for a crosslinking role for tenascins,” Structure, vol. 12, no. 8, pp. 1495–1506, 2004. View at Publisher · View at Google Scholar · View at Scopus
  79. S. Avram, D. Duda-Seiman, F. Borcan, B. Radu, C. Duda-Seiman, and D. Mihailescu, “Evaluation of antimicrobial activity of new mastoparan derivatives using QSAR and computational mutagenesis,” International Journal of Peptide Research and Therapeutics, vol. 17, no. 1, pp. 7–17, 2011. View at Publisher · View at Google Scholar · View at Scopus
  80. O. Calborean, M. Mernea, S. Avram, and D. F. Mihailescu, “Pharmacological descriptors related to the binding of Gp120 to CD4 corresponding to 60 representative HIV-1 strains,” Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 28, no. 5, pp. 1015–1025, 2013. View at Google Scholar
  81. S. Bhat and E. O. Purisima, “Molecular surface generation using a variable-radius solvent probe,” Proteins: Structure, Function and Genetics, vol. 62, no. 1, pp. 244–261, 2006. View at Publisher · View at Google Scholar · View at Scopus
  82. A. J. Li and R. Nussinov, “A set of van der Waals and coulombic radii of protein atoms for molecular and solvent-accessible surface calculation, packing evaluation, and docking,” Proteins, vol. 32, no. 1, pp. 111–127, 1998. View at Google Scholar
  83. T. I. Oprea, “Property distribution of drug-related chemical databases,” Journal of Computer-Aided Molecular Design, vol. 14, no. 3, pp. 251–264, 2000. View at Publisher · View at Google Scholar · View at Scopus
  84. A. L. Johnstone, G. W. Reierson, R. P. Smith, J. L. Goldberg, V. P. Lemmon, and J. L. Bixby, “A chemical genetic approach identifies piperazine antipsychotics as promoters of CNS neurite growth on inhibitory substrates,” Molecular and Cellular Neuroscience, vol. 50, no. 2, pp. 125–135, 2012. View at Google Scholar
  85. S. Avram, H. Berner, A. L. Milac, and P. Wolschann, “Quantitative structure—activity relationship studies on membrane receptors inhibition by antipsychotic drugs. Application to schizophrenia treatment,” Monatshefte für Chemie, vol. 139, no. 4, pp. 407–426, 2008. View at Publisher · View at Google Scholar · View at Scopus
  86. W. T. Carpenter Jr., “The deficit syndrome,” American Journal of Psychiatry, vol. 151, no. 3, pp. 327–329, 1994. View at Google Scholar · View at Scopus
  87. I. V. Vahia, N. M. Lanouette, S. Golshan et al., “Adding antidepressants to antipsychotics for treatment of subsyndromal depressive symptoms in schizophrenia: impact on positive and negative symptoms,” Indian Journal of Psychiatry, vol. 55, no. 2, pp. 144–148, 2013. View at Google Scholar
  88. S. Avram, A.-L. Milac, and D. Mihailescu, “3D-QSAR study indicates an enhancing effect of membrane ions on psychiatric drugs targeting serotonin receptor 5-HT1A,” Molecular BioSystems, vol. 8, no. 5, pp. 1418–1425, 2012. View at Publisher · View at Google Scholar · View at Scopus
  89. X.-H. Lu and D. S. Dwyer, “Second-generation antipsychotic drugs, olanzapine, quetiapine, and clozapine enhance neurite outgrowth in PC12 cells via PI3K/AKT, ERK, and pertussis toxin-sensitive pathways,” Journal of Molecular Neuroscience, vol. 27, no. 1, pp. 43–64, 2005. View at Publisher · View at Google Scholar · View at Scopus
  90. D. R. Donohoe, K. Weeks, E. J. Aamodt, and D. S. Dwyer, “Antipsychotic drugs alter neuronal development including ALM neuroblast migration and PLM axonal outgrowth in Caenorhabditis elegans,” International Journal of Developmental Neuroscience, vol. 26, no. 3-4, pp. 371–380, 2008. View at Publisher · View at Google Scholar · View at Scopus
  91. A. Zalesky, A. Fornito, M. L. Seal et al., “Disrupted axonal fiber connectivity in schizophrenia,” Biological Psychiatry, vol. 69, no. 1, pp. 80–89, 2011. View at Publisher · View at Google Scholar · View at Scopus
  92. H. Pantazopoulos, T.-U. W. Woo, M. P. Lim, N. Lange, and S. Berretta, “Extracellular matrix-glial abnormalities in the amygdala and entorhinal cortex of subjects diagnosed with schizophrenia,” Archives of General Psychiatry, vol. 67, no. 2, pp. 155–166, 2010. View at Publisher · View at Google Scholar · View at Scopus
  93. Y. Yamaguchi, “Lecticans: organizers of the brain extracellular matrix,” Cellular and Molecular Life Sciences, vol. 57, no. 2, pp. 276–289, 2000. View at Google Scholar · View at Scopus