Physiological and pathological roles of tissue plasminogen activator and its inhibitor neuroserpin in the nervous system

Frontiers in Cellular Neuroscience

Volumn 9, Issue OCT, 2015, Pages

  Lee, Tet Woo ^a,c   Tsang, Vicky W K ^a   Birch, Nigel P ^a,b  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

^b Universities of Auckland and Otago   (New Zealand)

^c UNIVERSITY OF OTAGO   (New Zealand)

Author keywords

Alzheimer s disease; Neurite growth; Neurodegeneration and neuroprotection; Neuronal migration; Neurovascular unit; Serine protease; Serpin; Synaptic plasticity

Indexed keywords

LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; MATRIX METALLOPROTEINASE; NEUROSERPIN; NITRIC OXIDE SYNTHASE; PLASMINOGEN ACTIVATOR INHIBITOR; TISSUE PLASMINOGEN ACTIVATOR; UROKINASE;

BLOOD BRAIN BARRIER; CELL MIGRATION; CENTRAL NERVOUS SYSTEM; HIPPOCAMPUS; LONG TERM DEPRESSION; LONG TERM POTENTIATION; NERVE CELL PLASTICITY; NERVE DEGENERATION; NERVE FIBER GROWTH; NEUROLOGIC DISEASE; NEUROPROTECTION; NONHUMAN; PROTEIN DEGRADATION; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION;

EID: 84944452157     PISSN: 16625102     EISSN: None     Source Type: Journal    
DOI: 10.3389/fncel.2015.00396     Document Type: Review

References (131)

1. Akassoglou, K., Kombrinck, K. W., Degen, J. L., and Strickland, S. (2000). Tissue plasminogen activator-mediated fibrinolysis protects against axonal degeneration and demyelination after sciatic nerve injury. J. Cell Biol. 149, 1157-1166. doi: 10.1083/jcb.149.5.1157
2. Baranes, D., Lederfein, D., Huang, Y. Y., Chen, M., Bailey, C. H., and Kandel, E. R. (1998). Tissue plasminogen activator contributes to the late phase of LTP and to synaptic growth in the hippocampal mossy fiber pathway. Neuron 21, 813-825. doi: 10.1016/S0896-6273(00)80597-8
3. Barker-Carlson, K., Lawrence, D. A., and Schwartz, B. S. (2002). Acyl-enzyme complexes between tissue-type plasminogen activator and neuroserpin are short-lived in vitro. J. Biol. Chem. 277, 46852-46857. doi: 10.1074/jbc.M207740200
4. Barnes, P., and Thomas, K. L. (2008). Proteolysis of proBDNF is a key regulator in the formation of memory. PLoS ONE 3:e3248. doi:10.1371/journal.pone.0003248
5. Basham, M. E., and Seeds, N. W. (2001). Plasminogen expression in the neonatal and adult mouse brain. J. Neurochem. 77, 318-325. doi: 10.1046/j.1471-4159.2001.t01-1-00239.x
6. Belorgey, D., Hägglöf, P., Onda, M., and Lomas, D. A. (2010). pH-dependent stability of neuroserpin is mediated by histidines 119 and 138; implications for the control of beta-sheet A and polymerization. Protein Sci. 19, 220-228. doi: 10.1002/pro.299
7. Benchenane, K., Castel, H., Boulouard, M., Bluthé, R., Fernandez-Monreal, M., Roussel, B. D., et al. (2007). Anti-NR1 N-terminal-domain vaccination unmasks the crucial action of tPA on NMDA-receptor-mediated toxicity and spatial memory. J. Cell Sci. 120, 578-585. doi: 10.1242/jcs.03354
8. Berger, P., Kozlov, S. V., Cinelli, P., Krüger, S. R., Vogt, L., and Sonderegger, P. (1999). Neuronal depolarization enhances the transcription of the neuronal serine protease inhibitor neuroserpin. Mol. Cell. Neurosci. 14, 455-467. doi:10.1006/mcne.1999.0804
9. Borges, V. M., Lee, T. W., Christie, D. L., and Birch, N. P. (2010). Neuroserpin regulates the density of dendritic protrusions and dendritic spine shape in cultured hippocampal neurons. J. Neurosci. Res. 88, 2610-2617. doi:10.1002/jnr.22428
10. Brennand, K. J., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., et al. (2011). Modelling schizophrenia using human induced pluripotent stem cells. Nature 473, 221-225. doi: 10.1038/nature09915
11. Bruno, M. A., and Cuello, A. C. (2006). Activity-dependent release of precursor nerve growth factor, conversion to mature nerve growth factor, and its degradation by a protease cascade. Proc. Natl. Acad. Sci. U.S.A. 103, 6735-6740. doi: 10.1073/pnas.0510645103
12. Bukhari, N., Torres, L., Robinson, J. K., and Tsirka, S. E. (2011). Axonal regrowth after spinal cord injury via chondroitinase and the tissue plasminogen activator (tPA)/plasmin system. J. Neurosci. 31, 14931-14943. doi:10.1523/JNEUROSCI.3339-11.2011
13. Calabresi, P., Napolitano, M., Centonze, D., Marfia, G. A., Gubellini, P., Teule, M. A., et al. (2000). Tissue plasminogen activator controls multiple forms of synaptic plasticity and memory. Eur. J. Neurosci. 12, 1002-1012. doi:10.1046/j.1460-9568.2000.00991.x
14. Cao, C., Lawrence, D. A., Li, Y., Von Arnim, C. A., Herz, J., Su, E. J., et al. (2006). Endocytic receptor LRP together with tPA and PAI-1 coordinates Mac-1-dependent macrophage migration. EMBO J. 25, 1860-1870. doi:10.1038/sj.emboj.7601082
15. Centonze, D., Napolitano, M., Saulle, E., Gubellini, P., Picconi, B., Martorana, A., et al. (2002). Tissue plasminogen activator is required for corticostriatal long-term potentiation. Eur. J. Neurosci. 16, 713-721. doi: 10.1046/j.1460-9568.2002.02106.x
16. Chen, Z. L., and Strickland, S. (1997). Neuronal death in the hippocampus is promoted by plasmin-catalyzed degradation of laminin. Cell 91, 917-925. doi:10.1016/S0092-8674(00)80483-3
17. Cinelli, P., Madani, R., Tsuzuki, N., Vallet, P., Arras, M., Zhao, C. N., et al. (2001). Neuroserpin, a neuroprotective factor in focal ischemic stroke. Mol. Cell. Neurosci. 18, 443-457. doi: 10.1006/mcne.2001.1028
18. Coutelier, M., Andries, S., Ghariani, S., Dan, B., Duyckaerts, C., Van Rijckevorsel, K., et al. (2008). Neuroserpin mutation causes electrical status epilepticus of slow-wave sleep. Neurology 71, 64-66. doi:10.1212/01.wnl.0000316306.08751.28
19. Davis, R. L., Shrimpton, A. E., Carrell, R. W., Lomas, D. A., Gerhard, L., Baumann, B., et al. (2002). Association between conformational mutations in neuroserpin and onset and severity of dementia. Lancet 359, 2242-2247. doi: 10.1016/S0140-6736(02)09293-0
20. Davis, R. L., Shrimpton, A. E., Holohan, P. D., Bradshaw, C., Feiglin, D., Collins, G. H., et al. (1999). Familial dementia caused by polymerization of mutant neuroserpin. Nature 401, 376-379. doi: 10.1038/43894
21. Fabbro, S., Schaller, K., and Seeds, N. W. (2011). Amyloid-beta levels are significantly reduced and spatial memory defects are rescued in a novel neuroserpin-deficient Alzheimer’s disease transgenic mouse model. J. Neurochem. 118, 928-938. doi: 10.1111/j.1471-4159.2011.07359.x
22. Fabbro, S., and Seeds, N. W. (2009). Plasminogen activator activity is inhibited while neuroserpin is up-regulated in the Alzheimer disease brain. J. Neurochem. 109, 303-315. doi: 10.1111/j.1471-4159.2009.05894.x
23. Fredriksson, L., Stevenson, T. K., Su, E. J., Ragsdale, M., Moore, S., Craciun, S., et al. (2015). Identification of a neurovascular signaling pathway regulating seizures in mice. Ann. Clin. Transl. Neurol. 2, 722-738. doi: 10.1002/acn3.209
24. Freeman, R., Niego, B., Croucher, D. R., Pedersen, L. O., and Medcalf, R. L. (2014). t-PA, but not desmoteplase, induces plasmin-dependent opening of a blood- brain barrier model under normoxic and ischaemic conditions. Brain Res. 1565, 63-73. doi: 10.1016/j.brainres.2014.03.027
25. Frey, U., Müller, M., and Kuhl, D. (1996). A different form of long-lasting potentiation revealed in tissue plasminogen activator mutant mice. J. Neurosci. 16, 2057-2063.
26. Friedman, G. C., and Seeds, N. W. (1994). Tissue plasminogen activator expression in the embryonic nervous system. Brain Res. Dev. Brain Res. 81, 41-49. doi: 10.1016/0165-3806(94)90066-3
27. Gaberel, T., Macrez, R., Gauberti, M., Montagne, A., Hebert, M., Petersen, K. U., et al. (2013). Immunotherapy blocking the tissue plasminogen activator-dependent activation of N-methyl-D-aspartate glutamate receptors improves hemorrhagic stroke outcome. Neuropharmacology 67, 267-271. doi:10.1016/j.neuropharm.2012.11.023
28. Gelderblom, M., Neumann, M., Ludewig, P., Bernreuther, C., Krasemann, S., Arunachalam, P., et al. (2013). Deficiency in serine protease inhibitor neuroserpin exacerbates ischemic brain injury by increased postischemic inflammation. PLoS ONE 8:e63118. doi: 10.1371/journal.pone.0063118
29. Gourfinkel-An, I., Duyckaerts, C., Camuzat, A., Meyrignac, C., Sonderegger, P., Baulac, M., et al. (2007). Clinical and neuropathologic study of a French family with a mutation in the neuroserpin gene. Neurology 69, 79-83. doi:10.1212/01.wnl.0000265052.99144.b5
30. Hagen, M. C., Murrell, J. R., Delisle, M. B., Andermann, E., Andermann, F., Guiot, M. C., et al. (2011). Encephalopathy with neuroserpin inclusion bodies presenting as progressive myoclonus epilepsy and associated with a novel mutation in the Proteinase Inhibitor 12 gene. Brain Pathol. 21, 575-582. doi:10.1111/j.1750-3639.2011.00481.x
31. Haile, W. B., Wu, J., Echeverry, R., Wu, F., An, J., and Yepes, M. (2012). Tissue- type plasminogen activator has a neuroprotective effect in the ischemic brain mediated by neuronal TNF-alpha. J. Cereb. Blood Flow Metab. 32, 57-69. doi:10.1038/jcbfm.2011.106
32. Hakak, Y., Walker, J. R., Li, C., Wong, W. H., Davis, K. L., Buxbaum, J. D., et al. (2001). Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc. Natl. Acad. Sci. U.S.A. 98, 4746-4751. doi: 10.1073/pnas.081071198
33. Hastings, G. A., Coleman, T. A., Haudenschild, C. C., Stefansson, S., Smith, E. P., Barthlow, R., et al. (1997). Neuroserpin, a brain-associated inhibitor of tissue plasminogen activator is localized primarily in neurons. Implications for the regulation of motor learning and neuronal survival. J. Biol. Chem. 272, 33062-33067. doi: 10.1074/jbc.272.52.33062
34. Hill, R. M., Parmar, P. K., Coates, L. C., Mezey, E., Pearson, J. F., and Birch, N. P. (2000). Neuroserpin is expressed in the pituitary and adrenal glands and induces the extension of neurite-like processes in AtT-20 cells. Biochem. J. 345(Pt 3), 595-601. doi: 10.1042/bj3450595
35. Hu, K., Yang, J., Tanaka, S., Gonias, S. L., Mars, W. M., and Liu, Y. (2006). Tissue- type plasminogen activator acts as a cytokine that triggers intracellular signal transduction and induces matrix metalloproteinase-9 gene expression. J. Biol. Chem. 281, 2120-2127. doi: 10.1074/jbc.M504988200
36. Huang, Y. Y., Bach, M. E., Lipp, H. P., Zhuo, M., Wolfer, D. P., Hawkins, R. D., et al. (1996). Mice lacking the gene encoding tissue-type plasminogen activator show a selective interference with late-phase long-term potentiation in both Schaffer collateral and mossy fiber pathways. Proc. Natl. Acad. Sci. U.S.A. 93, 8699-8704. doi: 10.1073/pnas.93.16.8699
37. Ishigami, S., Sandkvist, M., Tsui, F., Moore, E., Coleman, T. A., and Lawrence, D. A. (2007). Identification of a novel targeting sequence for regulated secretion in the serine protease inhibitor neuroserpin. Biochem. J. 402, 25-34. doi:10.1042/BJ20061170
38. Kaur, J., Zhao, Z., Klein, G. M., Lo, E. H., and Buchan, A. M. (2004). The neurotoxicity of tissue plasminogen activator? J. Cereb. Blood Flow Metab. 24, 945-963. doi: 10.1097/01.WCB.0000137868.50767.E8
39. Kim, Y. H., Park, J. H., Hong, S. H., and Koh, J. Y. (1999). Nonproteolytic neuroprotection by human recombinant tissue plasminogen activator. Science 284, 647-650. doi: 10.1126/science.284.5414.647
40. Kinghorn, K. J., Crowther, D. C., Sharp, L. K., Nerelius, C., Davis, R. L., Chang, H. T., et al. (2006). Neuroserpin binds Abeta and is a neuroprotective component of amyloid plaques in Alzheimer disease. J. Biol. Chem. 281, 29268-29277. doi:10.1074/jbc.M600690200
41. Krueger, S. R., Ghisu, G. P., Cinelli, P., Gschwend, T. P., Osterwalder, T., Wolfer, D. P., et al. (1997). Expression of neuroserpin, an inhibitor of tissue plasminogen activator, in the developing and adult nervous system of the mouse. J. Neurosci. 17, 8984-8996.
42. Kvajo, M., Albrecht, H., Meins, M., Hengst, U., Troncoso, E., Lefort, S., et al. (2004). Regulation of brain proteolytic activity is necessary for the in vivo function of NMDA receptors. J. Neurosci. 24, 9734-9743. doi: 10.1523/JNEUROSCI.3306-04.2004
43. Lebeurrier, N., Launay, S., Macrez, R., Maubert, E., Legros, H., Leclerc, A., et al. (2008). Anti-Mullerian-hormone-dependent regulation of the brain serine-protease inhibitor neuroserpin. J. Cell Sci. 121, 3357-3365. doi:10.1242/jcs.031872
44. Lee, H. Y., Hwang, I. Y., Im, H., Koh, J. Y., and Kim, Y. H. (2007a). Non-proteolytic neurotrophic effects of tissue plasminogen activator on cultured mouse cerebrocortical neurons. J. Neurochem. 101, 1236-1247. doi: 10.1111/j.1471-4159.2007.04417.x
45. Lee, S. R., Lok, J., Rosell, A., Kim, H. Y., Murata, Y., Atochin, D., et al. (2007b). Reduction of hippocampal cell death and proteolytic responses in tissue plasminogen activator knockout mice after transient global cerebral ischemia. Neuroscience 150, 50-57. doi: 10.1016/j.neuroscience.2007.06.029
46. Lee, T. W., Coates, L. C., and Birch, N. P. (2008). Neuroserpin regulates N-cadherin-mediated cell adhesion independently of its activity as an inhibitor of tissue plasminogen activator. J. Neurosci. Res. 86, 1243-1253. doi:10.1002/jnr.21592
47. Lee, T. W., Yang, A. S., Brittain, T., and Birch, N. P. (2015). An analysis approach to identify specific functional sites in orthologous proteins using sequence and structural information: application to neuroserpin reveals regions that differentially regulate inhibitory activity. Proteins 83, 135-152. doi:10.1002/prot.24711
48. Liot, G., Roussel, B. D., Lebeurrier, N., Benchenane, K., López-Atalaya, J. P., Vivien, D., et al. (2006). Tissue-type plasminogen activator rescues neurons from serum deprivation-induced apoptosis through a mechanism independent of its proteolytic activity. J. Neurochem. 98, 1458-1464. doi: 10.1111/j.1471-4159.2006.03982.x
49. Lochner, J. E., Honigman, L. S., Grant, W. F., Gessford, S. K., Hansen, A. B., Silverman, M. A., et al. (2006). Activity-dependent release of tissue plasminogen activator from the dendritic spines of hippocampal neurons revealed by live-cell imaging. J. Neurobiol. 66, 564-577. doi: 10.1002/neu.20250
50. Lochner, J. E., Kingma, M., Kuhn, S., Meliza, C. D., Cutler, B., and Scalettar, B. A. (1998). Real-time imaging of the axonal transport of granules containing a tissue plasminogen activator/green fluorescent protein hybrid. Mol. Biol. Cell 9, 2463-2476. doi: 10.1091/mbc.9.9.2463
51. Macrez, R., Bezin, L., Le Mauff, B., Ali, C., and Vivien, D. (2010). Functional occurrence of the interaction of tissue plasminogen activator with the NR1 Subunit of N-methyl-D-aspartate receptors during stroke. Stroke 41, 2950-2955. doi: 10.1161/STROKEAHA.110.592360
52. Madani, R., Hulo, S., Toni, N., Madani, H., Steimer, T., Muller, D., et al. (1999). Enhanced hippocampal long-term potentiation and learning by increased neuronal expression of tissue-type plasminogen activator in transgenic mice. EMBO J. 18, 3007-3012. doi: 10.1093/emboj/18.11.3007
53. Madani, R., Kozlov, S., Akhmedov, A., Cinelli, P., Kinter, J., Lipp, H. P., et al. (2003). Impaired explorative behavior and neophobia in genetically modified mice lacking or overexpressing the extracellular serine protease inhibitor neuroserpin. Mol. Cell. Neurosci. 23, 473-494. doi: 10.1016/S1044-7431(03)00077-0
54. Makarova, A., Mikhailenko, I., Bugge, T. H., List, K., Lawrence, D. A., and Strickland, D. K. (2003). The low density lipoprotein receptor-related protein modulates protease activity in the brain by mediating the cellular internalization of both neuroserpin and neuroserpin-tissue-type plasminogen activator complexes. J. Biol. Chem. 278, 50250-50258. doi:10.1074/jbc.M309150200
55. Martin, A. M., Kuhlmann, C., Trossbach, S., Jaeger, S., Waldron, E., Roebroek, A., et al. (2008). The functional role of the second NPXY motif of the LRP1 beta-chain in tissue-type plasminogen activator-mediated activation of N-methyl-D-aspartate receptors. J. Biol. Chem. 283, 12004-12013. doi:10.1074/jbc.M707607200
56. Masos, T., and Miskin, R. (1997). mRNAs encoding urokinase-type plasminogen activator and plasminogen activator inhibitor-1 are elevated in the mouse brain following kainate-mediated excitation. Brain Res. Mol. Brain Res. 47, 157-169. doi: 10.1016/S0169-328X(97)00040-5
57. Mataga, N., Mizuguchi, Y., and Hensch, T. K. (2004). Experience-dependent pruning of dendritic spines in visual cortex by tissue plasminogen activator. Neuron 44, 1031-1041. doi: 10.1016/j.neuron.2004.11.028
58. Mataga, N., Nagai, N., and Hensch, T. K. (2002). Permissive proteolytic activity for visual cortical plasticity. Proc. Natl. Acad. Sci. U.S.A. 99, 7717-7721. doi: 10.1073/pnas.102088899
59. Minor, K., Phillips, J., and Seeds, N. W. (2009). Tissue plasminogen activator promotes axonal outgrowth on CNS myelin after conditioned injury. J. Neurochem. 109, 706-715. doi: 10.1111/j.1471-4159.2009.05977.x
60. Miranda, E., Macleod, I., Davies, M. J., Pérez, J., Romisch, K., Crowther, D. C., et al. (2008). The intracellular accumulation of polymeric neuroserpin explains the severity of the dementia FENIB. Hum. Mol. Genet. 17, 1527-1539. doi:10.1093/hmg/ddn041
61. Nagappan, G., Zaitsev, E., Senatorov, V. V. Jr., Yang, J., Hempstead, B. L., and Lu, B. (2009). Control of extracellular cleavage of ProBDNF by high frequency neuronal activity. Proc. Natl. Acad. Sci. U.S.A. 106, 1267-1272. doi:10.1073/pnas.0807322106
62. Napolitano, M., Marfia, G. A., Vacca, A., Centonze, D., Bellavia, D., Di Marcotullio, L., et al. (1999). Modulation of gene expression following long-term synaptic depression in the striatum. Brain Res. Mol. Brain Res. 72, 89-96. doi:10.1016/S0169-328X(99)00213-2
63. Navarro-Yubero, C., Cuadrado, A., Sonderegger, P., and Muñoz, A. (2004). Neuroserpin is post-transcriptionally regulated by thyroid hormone. Brain Res. Mol. Brain Res. 123, 56-65. doi: 10.1016/j.molbrainres.2003.12.018
64. Neuhoff, H., Roeper, J., and Schweizer, M. (1999). Activity-dependent formation of perforated synapses in cultured hippocampal neurons. Eur. J. Neurosci. 11, 4241-4250. doi: 10.1046/j.1460-9568.1999.00856.x
65. Ng, K. S., Leung, H. W., Wong, P. T., and Low, C. M. (2012). Cleavage of the NR2B subunit amino terminus of N-methyl-D-aspartate (NMDA) receptor by tissue plasminogen activator: identification of the cleavage site and characterization of ifenprodil and glycine affinities on truncated NMDA receptor. J. Biol. Chem. 287, 25520-25529. doi: 10.1074/jbc.M112.374397
66. Nicole, O., Docagne, F., Ali, C., Margaill, I., Carmeliet, P., Mackenzie, E. T., et al. (2001). The proteolytic activity of tissue-plasminogen activator enhances NMDA receptor-mediated signaling. Nat. Med. 7, 59-64. doi: 10.1038/83358
67. Niego, B., and Medcalf, R. L. (2014). Plasmin-dependent modulation of the blood- brain barrier: a major consideration during tPA-induced thrombolysis? J. Cereb. Blood Flow Metab. 34, 1283-1296. doi:10.1038/jcbfm.2014.99
68. Noel, M., Norris, E. H., and Strickland, S. (2011). Tissue plasminogen activator is required for the development of fetal alcohol syndrome in mice. Proc. Natl. Acad. Sci. U.S.A. 108, 5069-5074. doi: 10.1073/pnas.1017608108
69. Norris, E. H., and Strickland, S. (2007). Modulation of NR2B-regulated contextual fear in the hippocampus by the tissue plasminogen activator system. Proc. Natl. Acad. Sci. U.S.A. 104, 13473-13478. doi: 10.1073/pnas.0705848104
70. Obiang, P., Macrez, R., Jullienne, A., Bertrand, T., Lesept, F., Ali, C., et al. (2012). GluN2D subunit-containing NMDA receptors control tissue plasminogen activator-mediated spatial memory. J. Neurosci. 32, 12726-12734. doi:10.1523/JNEUROSCI.6202-11.2012
71. Osterwalder, T., Cinelli, P., Baici, A., Pennella, A., Krueger, S. R., Schrimpf, S. P., et al. (1998). The axonally secreted serine proteinase inhibitor, neuroserpin, inhibits plasminogen activators and plasmin but not thrombin. J. Biol. Chem. 273, 2312-2321. doi: 10.1074/jbc.273.4.2312
72. Osterwalder, T., Contartese, J., Stoeckli, E. T., Kuhn, T. B., and Sonderegger, P. (1996). Neuroserpin, an axonally secreted serine protease inhibitor. EMBO J. 15, 2944-2953
73. Pang, P. T., Teng, H. K., Zaitsev, E., Woo, N. T., Sakata, K., Zhen, S., et al. (2004). Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science 306, 487-491. doi: 10.1126/science.1100135
74. Parathath, S. R., Parathath, S., and Tsirka, S. E. (2006). Nitric oxide mediates neurodegeneration and breakdown of the blood-brain barrier in tPA-dependent excitotoxic injury in mice. J. Cell Sci. 119, 339-349. doi:10.1242/jcs.02734
75. Park, L., Gallo, E. F., Anrather, J., Wang, G., Norris, E. H., Paul, J., et al. (2008). Key role of tissue plasminogen activator in neurovascular coupling. Proc. Natl. Acad. Sci. U.S.A. 105, 1073-1078. doi: 10.1073/pnas.0708823105
76. Parmar, P. K., Coates, L. C., Pearson, J. F., Hill, R. M., and Birch, N. P. (2002). Neuroserpin regulates neurite outgrowth in nerve growth factor-treated PC12 cells. J. Neurochem. 82, 1406-1415. doi: 10.1046/j.1471-4159.2002.01100.x
77. Parmer, R. J., Mahata, M., Mahata, S., Sebald, M. T., O’connor, D. T., and Miles, L. A. (1997). Tissue plasminogen activator (t-PA) is targeted to the regulated secretory pathway. Catecholamine storage vesicles as a reservoir for the rapid release of t-PA. J. Biol. Chem. 272, 1976-1982. doi: 10.1074/jbc.272.3.1976
78. Pawlak, R., Magarinos, A. M., Melchor, J., McEwen, B., and Strickland, S. (2003). Tissue plasminogen activator in the amygdala is critical for stress-induced anxiety-like behavior. Nat. Neurosci. 6, 168-174. doi: 10.1038/nn998
79. Pawlak, R., Melchor, J. P., Matys, T., Skrzypiec, A. E., and Strickland, S. (2005a). Ethanol-withdrawal seizures are controlled by tissue plasminogen activator via modulation of NR2B-containing NMDA receptors. Proc. Natl. Acad. Sci. U.S.A. 102, 443-448. doi: 10.1073/pnas.0406454102
80. Pawlak, R., Nagai, N., Urano, T., Napiorkowska-Pawlak, D., Ihara, H., Takada, Y., et al. (2002). Rapid, specific and active site-catalyzed effect of tissue-plasminogen activator on hippocampus-dependent learning in mice. Neuroscience 113, 995-1001. doi: 10.1016/S0306-4522(02)00166-5
81. Pawlak, R., Rao, B. S., Melchor, J. P., Chattarji, S., McEwen, B., and Strickland, S. (2005b). Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus. Proc. Natl. Acad. Sci. USA. 102, 18201-18206. doi: 10.1073/pnas.0509232102
82. Pittman, R. N., and Dibenedetto, A. J. (1995). PC12 cells overexpressing tissue plasminogen activator regenerate neurites to a greater extent and migrate faster than control cells in complex extracellular matrix. J. Neurochem. 64, 566-575. doi: 10.1046/j.1471-4159.1995.64020566.x
83. Pittman, R. N., Ivins, J. K., and Buettner, H. M. (1989). Neuronal plasminogen activators: cell surface binding sites and involvement in neurite outgrowth. J. Neurosci. 9, 4269-4286.
84. Qian, Z., Gilbert, M. E., Colicos, M. A., Kandel, E. R., and Kuhl, D. (1993). Tissue-plasminogen activator is induced as an immediate-early gene during seizure, kindling and long-term potentiation. Nature 361, 453-457. doi:10.1038/361453a0
85. Reinhard, E., Suidan, H. S., Pavlik, A., and Monard, D. (1994). Glia-derived nexin/protease nexin-1 is expressed by a subset of neurons in the rat brain. J. Neurosci. Res. 37, 256-270. doi: 10.1002/jnr.490370211
86. Ricagno, S., Caccia, S., Sorrentino, G., Antonini, G., and Bolognesi, M. (2009). Human neuroserpin: structure and time-dependent inhibition. J. Mol. Biol. 388, 109-121. doi: 10.1016/j.jmb.2009.02.056
87. Rodríguez-González, R., Agulla, J., Pérez-Mato, M., Sobrino, T., and Castillo, J. (2011). Neuroprotective effect of neuroserpin in rat primary cortical cultures after oxygen and glucose deprivation and tPA. Neurochem. Int. 58, 337-343. doi: 10.1016/j.neuint.2010.12.006
88. Rogove, A. D., Siao, C., Keyt, B., Strickland, S., and Tsirka, S. E. (1999). Activation of microglia reveals a non-proteolytic cytokine function for tissue plasminogen activator in the central nervous system. J. Cell Sci. 112 (Pt 22), 4007-4016
89. Rogove, A. D., and Tsirka, S. E. (1998). Neurotoxic responses by microglia elicited by excitotoxic injury in the mouse hippocampus. Curr. Biol. 8, 19-25. doi:10.1016/S0960-9822(98)70016-8
90. Samson, A. L., Nevin, S. T., Croucher, D., Niego, B., Daniel, P. B., Weiss, T. W., et al. (2008). Tissue-type plasminogen activator requires a co-receptor to enhance NMDA receptor function. J. Neurochem. 107, 1091-1101. doi:10.1111/j.1471-4159.2008.05687.x
91. Sappino, A. P., Madani, R., Huarte, J., Belin, D., Kiss, J. Z., Wohlwend, A., et al. (1993). Extracellular proteolysis in the adult murine brain. J. Clin. Invest. 92, 679-685. doi: 10.1172/JCI116637
92. Sashindranath, M., Sales, E., Daglas, M., Freeman, R., Samson, A. L., Cops, E. J., et al. (2012). The tissue-type plasminogen activator-plasminogen activator inhibitor 1 complex promotes neurovascular injury in brain trauma: evidence from mice and humans. Brain 135, 3251-3264. doi: 10.1093/brain/aws178
93. Sawdey, M. S., and Loskutoff, D. J. (1991). Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo. Tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-alpha, and transforming growth factor-beta. J. Clin. Invest. 88, 1346-1353. doi:10.1172/JCI115440
94. Scott, R. W., Bergman, B. L., Bajpai, A., Hersh, R. T., Rodriguez, H., Jones, B. N., et al. (1985). Protease nexin. Properties and a modified purification procedure. J. Biol. Chem. 260, 7029-7034.
95. Seeds, N. W., Basham, M. E., and Ferguson, J. E. (2003). Absence of tissue plasminogen activator gene or activity impairs mouse cerebellar motor learning. J. Neurosci. 23, 7368-7375.
96. Seeds, N. W., Basham, M. E., and Haffke, S. P. (1999). Neuronal migration is retarded in mice lacking the tissue plasminogen activator gene. Proc. Natl. Acad. Sci. U.S.A. 96, 14118-14123. doi: 10.1073/pnas.96.24.14118
97. Shi, Y., Mantuano, E., Inoue, G., Campana, W. M., and Gonias, S. L. (2009). Ligand binding to LRP1 transactivates Trk receptors by a Src family kinase-dependent pathway. Sci. Signal 2, ra18. doi: 10.1126/scisignal.2000188
98. Siao, C. J., and Tsirka, S. E. (2002). Tissue plasminogen activator mediates microglial activation via its finger domain through annexin II. J. Neurosci. 22, 3352-3358.
99. Siconolfi, L. B., and Seeds, N. W. (2001). Mice lacking tPA, uPA, or plasminogen genes showed delayed functional recovery after sciatic nerve crush. J. Neurosci. 21, 4348-4355.
100. Siconolfi, L. B., and Seeds, N. W. (2003). Mice lacking tissue plasminogen activator and urokinase plasminogen activator genes show attenuated matrix metalloproteases activity after sciatic nerve crush. J. Neurosci. Res. 74, 430-434. doi: 10.1002/jnr.10786
101. Silverman, M. A., Johnson, S., Gurkins, D., Farmer, M., Lochner, J. E., Rosa, P., et al. (2005). Mechanisms of transport and exocytosis of dense-core granules containing tissue plasminogen activator in developing hippocampal neurons. J. Neurosci. 25, 3095-3106. doi: 10.1523/JNEUROSCI.4694-04.2005
102. Simonin, Y., Charron, Y., Sonderegger, P., Vassalli, J. D., and Kato, A. C. (2006). An inhibitor of serine proteases, neuroserpin, acts as a neuroprotective agent in a mouse model of neurodegenerative disease. J. Neurosci. 26, 10614-10619. doi:10.1523/JNEUROSCI.3582-06.2006
103. Strickland, S. (2001). Tissue plasminogen activator in nervous system function and dysfunction. Thromb. Haemost. 86, 138-143.
104. Su, E. J., Fredriksson, L., Geyer, M., Folestad, E., Cale, J., Andrae, J., et al. (2008). Activation of PDGF-CC by tissue plasminogen activator impairs blood-brain barrier integrity during ischemic stroke. Nat. Med. 14, 731-737. doi:10.1038/nm1787
105. Sumii, T., and Lo, E. H. (2002). Involvement of matrix metalloproteinase in thrombolysis-associated hemorrhagic transformation after embolic focal ischemia in rats. Stroke 33, 831-836. doi: 10.1161/hs0302.104542
106. Takao, M., Benson, M. D., Murrell, J. R., Yazaki, M., Piccardo, P., Unverzagt, F. W., et al. (2000). Neuroserpin mutation S52R causes neuroserpin accumulation in neurons and is associated with progressive myoclonus epilepsy. J. Neuropathol. Exp. Neurol. 59, 1070-1086.
107. Teesalu, T., Kulla, A., Simisker, A., Sirén, V., Lawrence, D. A., Asser, T., et al. (2004). Tissue plasminogen activator and neuroserpin are widely expressed in the human central nervous system. Thromb. Haemost. 92, 358-368. doi:10.1160/th02-12-0310
108. Tsang, V. W. K., Young, D., During, M. J., and Birch, N. P. (2014). AAV- mediated overexpression of neuroserpin in the hippocampus decreases PSD-95 expression but does not affect hippocampal-dependent learning and memory. PLoS ONE 9:e91050. doi: 10.1371/journal.pone.0091050
109. Tsirka, S. E., Gualandris, A., Amaral, D. G., and Strickland, S. (1995). Excitotoxin- induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. Nature 377, 340-344. doi: 10.1038/377340a0
110. Tsirka, S. E., Rogove, A. D., Bugge, T. H., Degen, J. L., and Strickland, S. (1997). An extracellular proteolytic cascade promotes neuronal degeneration in the mouse hippocampus. J. Neurosci. 17, 543-552.
111. Valiente, M., Obenauf, A. C., Jin, X., Chen, Q., Zhang, X. H., Lee, D. J., et al. (2014). Serpins promote cancer cell survival and vascular co-option in brain metastasis. Cell 156, 1002-1016. doi: 10.1016/j.cell.2014.01.040
112. Vanlandingham, J. W., Cekic, M., Cutler, S. M., Hoffman, S. W., Washington, E. R., Johnson, S. J., et al. (2008). Progesterone and its metabolite allopregnanolone differentially regulate hemostatic proteins after traumatic brain injury. J. Cereb. Blood Flow Metab. 28, 1786-1794. doi: 10.1038/jcbfm.2008.73
113. Vawter, M. P., Shannon Weickert, C., Ferran, E., Matsumoto, M., Overman, K., Hyde, T. M., et al. (2004). Gene expression of metabolic enzymes and a protease inhibitor in the prefrontal cortex are decreased in schizophrenia. Neurochem. Res. 29, 1245-1255. doi: 10.1023/B:NERE.0000023611.99452.47
114. Wang, X., Lee, S. R., Arai, K., Lee, S. R., Tsuji, K., Rebeck, G. W., et al. (2003). Lipoprotein receptor-mediated induction of matrix metalloproteinase by tissue plasminogen activator. Nat. Med. 9, 1313-1317. doi: 10.1038/nm926
115. Wang, X., Tsuji, K., Lee, S. R., Ning, M., Furie, K. L., Buchan, A. M., et al. (2004). Mechanisms of hemorrhagic transformation after tissue plasminogen activator reperfusion therapy for ischemic stroke. Stroke 35, 2726-2730. doi:10.1161/01.STR.0000143219.16695.af
116. Wang, Y. F., Tsirka, S. E., Strickland, S., Stieg, P. E., Soriano, S. G., and Lipton, S. A. (1998). Tissue plasminogen activator (tPA) increases neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice. Nat. Med. 4, 228-231. doi: 10.1038/nm0298-228
117. Wannier-Morino, P., Rager, G., Sonderegger, P., and Grabs, D. (2003). Expression of neuroserpin in the visual cortex of the mouse during the developmental critical period. Eur. J. Neurosci. 17, 1853-1860. doi:10.1046/j.1460-9568.2003.02628.x
118. Ware, J. H., Dibenedetto, A. J., and Pittman, R. N. (1995). Localization of tissue plasminogen activator mRNA in adult rat brain. Brain Res. Bull. 37, 275-281. doi: 10.1016/0361-9230(95)00008-3
119. Woo, N. H., Teng, H. K., Siao, C. J., Chiaruttini, C., Pang, P. T., Milner, T. A., et al. (2005). Activation of p75NTR by proBDNF facilitates hippocampal long-term depression. Nat. Neurosci. 8, 1069-1077. doi: 10.1038/nn1510
120. Wu, F., Echeverry, R., Wu, J., An, J., Haile, W. B., Cooper, D. S., et al. (2013). Tissue-type plasminogen activator protects neurons from excitotoxin-induced cell death via activation of the ERK1/2-CREB-ATF3 signaling pathway. Mol. Cell. Neurosci. 52, 9-19. doi: 10.1016/j.mcn.2012.10.001
121. Wu, F., Wu, J., Nicholson, A. D., Echeverry, R., Haile, W. B., Catano, M., et al. (2012). Tissue-type plasminogen activator regulates the neuronal uptake of glucose in the ischemic brain. J. Neurosci. 32, 9848-9858. doi:10.1523/JNEUROSCI.1241-12.2012
122. Wu, J., Echeverry, R., Guzman, J., and Yepes, M. (2010). Neuroserpin protects neurons from ischemia-induced plasmin-mediated cell death independently of tissue-type plasminogen activator inhibition. Am. J. Pathol. 177, 2576-2584. doi: 10.2353/ajpath.2010.100466
123. Wu, Y. P., Siao, C. J., Lu, W., Sung, T. C., Frohman, M. A., Milev, P., et al. (2000). The tissue plasminogen activator (tPA)/plasmin extracellular proteolytic system regulates seizure-induced hippocampal mossy fiber outgrowth through a proteoglycan substrate. J. Cell Biol. 148, 1295-1304. doi: 10.1083/jcb.148.6.1295
124. Yamada, M., Takahashi, K., Ukai, W., Hashimoto, E., Saito, T., and Yamada, M. (2010). Neuroserpin is expressed in early stage of neurogenesis in adult rat hippocampus. Neuroreport 21, 138-142. doi:10.1097/WNR.0b013e3283350b24
125. Yepes, M., Sandkvist, M., Moore, E. G., Bugge, T. H., Strickland, D. K., and Lawrence, D. A. (2003). Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein. J. Clin. Invest. 112, 1533-1540. doi: 10.1172/JCI200319212
126. Yepes, M., Sandkvist, M., Wong, M. K., Coleman, T. A., Smith, E., Cohan, S. L., et al. (2000). Neuroserpin reduces cerebral infarct volume and protects neurons from ischemia-induced apoptosis. Blood 96, 569-576.
127. Yi, J. S., Kim, Y. H., and Koh, J. Y. (2004). Infarct reduction in rats following intraventricular administration of either tissue plasminogen activator (tPA) or its non-protease mutant S478A-tPA. Exp. Neurol. 189, 354-360. doi:10.1016/j.expneurol.2004.05.032
128. Zhang, C., An, J., Strickland, D. K., and Yepes, M. (2009). The low-density lipoprotein receptor-related protein 1 mediates tissue-type plasminogen activator-induced microglial activation in the ischemic brain. Am. J. Pathol. 174, 586-594. doi: 10.2353/ajpath.2009.080661
129. Zhang, Z., Zhang, L., Yepes, M., Jiang, Q., Li, Q., Arniego, P., et al. (2002). Adjuvant treatment with neuroserpin increases the therapeutic window for tissue-type plasminogen activator administration in a rat model of embolic stroke. Circulation 106, 740-745. doi: 10.1161/01.CIR.0000023942.10849.41
130. Zhuo, M., Holtzman, D. M., Li, Y., Osaka, H., DeMaro, J., Jacquin, M., et al. (2000). Role of tissue plasminogen activator receptor LRP in hippocampal long-term potentiation. J. Neurosci. 20, 542-549.
131. Zou, T., Ling, C., Xiao, Y., Tao, X., Ma, D., Chen, Z. L., et al. (2006). Exogenous tissue plasminogen activator enhances peripheral nerve regeneration and functional recovery after injury in mice. J. Neuropathol. Exp. Neurol. 65, 78-86. doi: 10.1097/01.jnen.0000195942.25163.f5