Startseite Kallikrein-related peptidase 6 orchestrates astrocyte form and function through proteinase activated receptor-dependent mechanisms
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Kallikrein-related peptidase 6 orchestrates astrocyte form and function through proteinase activated receptor-dependent mechanisms

  • Hyesook Yoon , Maja Radulovic und Isobel A. Scarisbrick EMAIL logo
Veröffentlicht/Copyright: 31. März 2018

Abstract

Kallikrein-related peptidase 6 (Klk6) is the most abundant serine proteinase in the adult central nervous system (CNS), yet we know little regarding its physiological roles or mechanisms of action. Levels of Klk6 in the extracellular environment are dynamically regulated in CNS injury and disease positioning this secreted enzyme to affect cell behavior by potential receptor dependent and independent mechanisms. Here we show that recombinant Klk6 evokes increases in intracellular Ca2+ in primary astrocyte monolayer cultures through activation of proteinase activated receptor 1 (PAR1). In addition, Klk6 promoted a condensation of astrocyte cortical actin leading to an elongated stellate shape and multicellular aggregation in a manner that was dependent on the presence of either PAR1 or PAR2. Klk6-evoked changes in astrocyte shape were accompanied by translocation of β-catenin from the plasma membrane to the cytoplasm. These data are exciting because they demonstrate that Klk6 can influence astrocyte plasticity through receptor-dependent mechanisms. Furthermore, this study expands our understanding of the mechanisms by which kallikreins can contribute to neural homeostasis and remodeling and point to both PAR1 and PAR2 as new therapeutic targets to modulate astrocyte form and function.

Award Identifier / Grant number: R01NS052741

Award Identifier / Grant number: RG3367

Funding statement: These studies were supported by National Institute of Neurological Disorders and Stroke, R01NS052741 and (Funder Id: 10.13039/100000065) RG3367 from the National Multiple Sclerosis Society to I.A.S. The authors gratefully acknowledge Dr. Michael Blaber for kindly providing the recombinant Klk6.

References

Allen, M., Ghosh, S., Ahern, G.P., Villapol, S., Maguire-Zeiss, K.A., and Conant, K. (2016). Protease induced plasticity: matrix metalloproteinase-1 promotes neurostructural changes through activation of protease activated receptor 1. Sci. Rep. 6, 35497.10.1038/srep35497Suche in Google Scholar PubMed PubMed Central

Anderson, M.A., Ao, Y., and Sofroniew, M.V. (2014). Heterogeneity of reactive astrocytes. Neurosci. Lett. 565, 23–29.10.1016/j.neulet.2013.12.030Suche in Google Scholar PubMed PubMed Central

Angelo, P.F., Lima, A.R., Alves, F.M., Blaber, S.I., Scarisbrick, I.A., Blaber, M., Juliano, L., and Juliano, M.A. (2006). Substrate specificity of human kallikrein 6: salt and glycosaminoglycan activation effects. J. Biol. Chem. 281, 3116–3126.10.1074/jbc.M510096200Suche in Google Scholar PubMed

Anisowicz, A., Sotiropoulou, G., Stenman, G., Mok, S.C., and Sager, R. (1996). A novel protease homolog differentially expressed in breast and ovarian cancer. Mol. Med. 2, 624–636.10.1007/BF03401646Suche in Google Scholar

Ashby, E.L., Kehoe, P.G., and Love, S. (2010). Kallikrein-related peptidase 6 in Alzheimer’s disease and vascular dementia. Brain Res. 1363, 1–10.10.1016/j.brainres.2010.09.017Suche in Google Scholar PubMed

Bernett, M.J., Blaber, S.I., Scarisbrick, I.A., Dhanarajan, P., Thompson, S.M., and Blaber, M. (2002). Crystal structure and biochemical characterization of human kallikrein 6 reveals that a trypsin-like kallikrein is expressed in the central nervous system. J. Biol. Chem. 277, 24562–24570.10.1074/jbc.M202392200Suche in Google Scholar PubMed

Blaber, S.I., Scarisbrick, I.A., Bernett, M.J., Dhanarajan, P., Seavy, M.A., Jin, Y., Schwartz, M.A., Rodriguez, M., and Blaber, M. (2002). Enzymatic properties of rat myelencephalon-specific protease. Biochemistry 41, 1165–1173.10.1021/bi015781aSuche in Google Scholar PubMed

Blaber, S.I., Ciric, B., Christophi, G.P., Bernett, M.J., Blaber, M., Rodriguez, M., and Scarisbrick, I.A. (2004). Targeting kallikrein 6-proteolysis attenuates CNS inflammatory disease. FASEB J. 19, 920–922.10.1096/fj.03-1212fjeSuche in Google Scholar PubMed

Borgono, C.A., Miacovos, M.P., and Diamandis, E.P. (2004). Human tissue kallikreins: physiologic roles and applications in cancer. Mol. Cancer Res. 2, 257–280.10.1158/1541-7786.257.2.5Suche in Google Scholar

Boven, L.A., Vergnolle, N., Henry, S.D., Silva, C., Imai, Y., Holden, J., Warren, K., Hollenberg, M.D., and Power, C. (2003). Up-regulation of proteinase-activated receptor 1 expression in astrocytes during HIV encephalitis. J. Immunol. 170, 2638–2646.10.4049/jimmunol.170.5.2638Suche in Google Scholar PubMed

Burda, J.E., Radulovic, M., Yoon, H., and Scarisbrick, I. A. (2013). Critical role for PAR1 in kallikrein 6-mediated oligodendrogliopathy. Glia 61, 1456–1470.10.1002/glia.22534Suche in Google Scholar

Citron, B.A., Smirnova, I.V., Arnold, P.M., and Festoff, B.W. (2000). Upregulation of neurotoxic serine proteases, prothrombin, and protease-activated receptor 1 early after spinal cord injury. J. Neurotrauma. 17, 1191–1203.10.1089/neu.2000.17.1191Suche in Google Scholar

Diamandis, E.P., Yousef, G.M., Petraki, C., and Soosaipillai, A. R. (2000). Human kallikrein 6 as a biomarker of alzheimer’s disease. Clin. Biochem. 33, 663–667.10.1016/S0009-9120(00)00185-5Suche in Google Scholar

Dong, Y., Tan, O.L., Loessner, D., Stephens, C., Walpole, C., Boyle, G.M., Parsons, P.G., and Clements, J.A. (2010). Kallikrein-related peptidase 7 promotes multicellular aggregation via the α(5)β(1) integrin pathway and paclitaxel chemoresistance in serous epithelial ovarian carcinoma. Cancer Res. 70, 2624–2633.10.1158/0008-5472.CAN-09-3415Suche in Google Scholar PubMed

Dong, Y., Stephens, C., Walpole, C., Swedberg, J.E., Boyle, G.M., Parsons, P.G., McGuckin, M.A., Harris, J.M., and Clements, J.A. (2013). Paclitaxel resistance and multicellular spheroid formation are induced by kallikrein-related peptidase 4 in serous ovarian cancer cells in an ascites mimicking microenvironment. PLoS One 8, e57056.10.1371/journal.pone.0057056Suche in Google Scholar PubMed PubMed Central

Drucker, K.L., Paulsen, A.R., Giannini, C., Decker, P.A., Blaber, S.I., Blaber, M., Uhm, J.H., O’Neill, B.P., Jenkins, R.B., and Scarisbrick, I.A. (2013). Clinical significance and novel mechanism of action of kallikrein 6 in glioblastoma. Neuro. Oncol. 15, 305–318.10.1093/neuonc/nos313Suche in Google Scholar PubMed PubMed Central

Drucker, K.L., Gianinni, C., Decker, P.A., Diamandis, E.P., and Scarisbrick, I.A. (2015). Prognostic significance of multiple kallikreins in high-grade astrocytoma. BMC Cancer 15, 565.10.1186/s12885-015-1566-5Suche in Google Scholar PubMed PubMed Central

Farmer, W.T. and Murai, K. (2017). Resolving astrocyte heterogeneity in the CNS. Front Cell Neurosci. 11, 300.10.3389/fncel.2017.00300Suche in Google Scholar PubMed PubMed Central

Halassa, M.M., Dal Maschio, M., Beltramo, R., Haydon, P.G., Benfenati, F., and Fellin, T. (2010). Integrated brain circuits: neuron-astrocyte interaction in sleep-related rhythmogenesis. ScientificWorldJ. 10, 1634–1645.10.1100/tsw.2010.130Suche in Google Scholar PubMed PubMed Central

Hamby, M.E., Coppola, G., Ao, Y., Geschwind, D.H., Khakh, B.S., and Sofroniew, M.V. (2012). Inflammatory mediators alter the astrocyte transcriptome and calcium signaling elicited by multiple G-protein-coupled receptors. J. Neurosci. 32, 14489–14510.10.1523/JNEUROSCI.1256-12.2012Suche in Google Scholar PubMed PubMed Central

Iadecola, C. and Nedergaard, M. (2007). Glial regulation of the cerebral microvasculature. Nat. Neurosci. 10, 1369–1376.10.1038/nn2003Suche in Google Scholar

Iwata, A., Maruyama, M., Akagi, T., Hashikawa, T., Kanazawa, I., Tsuji, S., and Nukina, N. (2003). Alpha-synuclein degradation by serine protease neurosin: implication for pathogenesis of synucleinopathies. Hum. Mol. Genet. 12, 2625–2635.10.1093/hmg/ddg283Suche in Google Scholar

Junge, C.E., Sugawara, T., Mannaioni, G., Alagarsamy, S., Conn, P.J., Brat, D.J., Chan, P.H., and Traynelis, S.F. (2003). The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia. Proc. Natl. Acad. Sci. USA 100, 13019–13024.10.1073/pnas.2235594100Suche in Google Scholar

Junge, C.E., Lee, C.J., Hubbard, K.B., Zhang, Z., Olson, J.J., Hepler, J.R., Brat, D.J., and Traynelis, S.F. (2004). Protease-activated receptor-1 in human brain: localization and functional expression in astrocytes. Exp. Neurol. 188, 94–103.10.1016/j.expneurol.2004.02.018Suche in Google Scholar

Kalluri, R. and Weinberg, R.A. (2009). The basics of epithelial-mesenchymal transition. J. Clin. Invest. 119, 1420–1428.10.1172/JCI39104Suche in Google Scholar

Kasai, T., Tokuda, T., Yamaguchi, N., Watanabe, Y., Kametani, F., Nakagawa, M., and Mizuno, T. (2008). Cleavage of normal and pathological forms of alpha-synuclein by neurosin in vitro. Neurosci. Lett. 436, 52–56.10.1016/j.neulet.2008.02.057Suche in Google Scholar

Laxmikanthan, G., Blaber, S.I., Bernett, M.J., Scarisbrick, I.A., Juliano, M.A., and Blaber, M. (2005). 1.70 Å X-ray structure of human apo kallikrein 1: structural changes upon peptide inhibitor/substrate binding. Proteins 58, 802–814.10.1002/prot.20368Suche in Google Scholar

Little, S.P., Dixon, E.P., Norris, F., Buckley, W., Becker, G.W., Johnson, M., Dobbins, J.R., Wyrick, T., Miller, J.R., MacKellar, W., et al. (1997). Zyme, a novel and potentially amyloidogenic enzyme cDNA isolated from Alzheimer’s disease brain. J. Biol. Chem. 272, 25135–25142.10.1074/jbc.272.40.25135Suche in Google Scholar

Magklara, A., Mellati, A.A., Wasney, G.A., Little, S.P., Sotiropoulou, G., Becker, G.W., and Diamandis, E.P. (2003). Characterization of the enzymatic activity of human kallikrein 6: autoactivation, substrate specificity, and regulation by inhibitors. Biochem. Biophys. Res. Commun. 307, 948–955.10.1016/S0006-291X(03)01271-3Suche in Google Scholar

Morel, L., Chiang, M.S.R., Higashimori, H., Shoneye, T., Iyer, L.K., Yelick, J., Tai, A. and Yang, Y. (2017). Molecular and functional properties of regional astrocytes in the adult brain. J. Neurosci. 37, 8706–8717.10.1523/JNEUROSCI.3956-16.2017Suche in Google Scholar PubMed PubMed Central

Nakanishi-Matsui, M., Zheng, Y.W., Sulciner, D.J., Weiss, E.J., Ludeman, M.J., and Coughlin, S.R. (2000). PAR3 is a cofactor for PAR4 activation by thrombin. Nature 404, 609–613.10.1038/35007085Suche in Google Scholar PubMed

Nicole, O., Goldshmidt, A., Hamill, C.E., Sorensen, S.D., Sastre, A., Lyuboslavsky, P., Hepler, J.R., McKeon, R.J., and Traynelis, S. F. (2005). Activation of protease-activated receptor-1 triggers astrogliosis after brain injury. J. Neurosci. 25, 4319–4329.10.1523/JNEUROSCI.5200-04.2005Suche in Google Scholar PubMed PubMed Central

Noorbakhsh, F., Vergnolle, N., Hollenberg, M.D., and Power, C. (2003). Proteinase-activated receptors in the nervous system. Nat. Rev. Neurosci. 4, 981–990.10.1038/nrn1255Suche in Google Scholar PubMed

Noorbakhsh, F., Vergnolle, N., McArthur, J.C., Silva, C., Vodjgani, M., Andrade-Gordon, P., Hollenberg, M.D., and Power, C. (2005). Proteinase-activated receptor-2 induction by neuroinflammation prevents neuronal death during HIV infection. J. Immunol. 174, 7320–7329.10.4049/jimmunol.174.11.7320Suche in Google Scholar PubMed

Noorbakhsh, F., Tsutsui, S., Vergnolle, N., Boven, L.A., Shariat, N., Vodjgani, M., Warren, K.G., Andrade-Gordon, P., Hollenberg, M.D., and Power, C. (2006). Proteinase-activated receptor 2 modulates neuroinflammation in experimental autoimmune encephalomyelitis and multiple sclerosis. J. Exp. Med. 203, 425–435.10.1084/jem.20052148Suche in Google Scholar PubMed PubMed Central

Ogawa, K., Yamada, T., Tsujioka, Y., Taguchi, J., Takahashi, M., Tsuboi, Y., Fujino, Y., Nakajima, M., Yamamoto, T., Akatsu, H., et al. (2000). Localization of a novel type trypsin-like serine protease, neurosin, in brain tissues of Alzheimer’s disease and Parkinson’s disease. Psychiatry Clin. Neurosci. 54, 419–426.10.1046/j.1440-1819.2000.00731.xSuche in Google Scholar PubMed

Oikonomopoulou, K., Hansen, K.K., Saifeddine, M., Tea, I., Blaber, M., Blaber, S.I., Scarisbrick, I., Andrade-Gordon, P., Cottrell, G.S., Bunnett, N.W., et al. (2006a). Proteinase-activated receptors, targets for kallikrein signaling. J. Biol. Chem. 281, 32095–32112.10.1074/jbc.M513138200Suche in Google Scholar PubMed

Oikonomopoulou, K., Hansen, K.K., Saifeddine, M., Vergnolle, N., Tea, I., Blaber, M., Blaber, S.I., Scarisbrick, I., Diamandis, E.P., and Hollenberg, M.D. (2006b). Kallikrein-mediated cell signalling: targeting proteinase-activated receptors (PARs). Biol. Chem. 387, 817–824.10.1515/BC.2006.104Suche in Google Scholar PubMed

Ostrowska, E. and Reiser, G. (2008). The protease-activated receptor-3 (PAR-3) can signal autonomously to induce interleukin-8 release. Cell Mol. Life Sci. 65, 970–981.10.1007/s00018-008-7555-ySuche in Google Scholar PubMed

Pampalakis, G., Sykioti, V.S., Ximerakis, M., Stefanakou-Kalakou, I., Melki, R., Vekrellis, K., and Sotiropoulou, G. (2017). KLK6 proteolysis is implicated in the turnover and uptake of extracellular alpha-synuclein species. Oncotarget 8, 14502–14515.10.18632/oncotarget.13264Suche in Google Scholar PubMed PubMed Central

Panos, M., Christophi, G.P., Rodriguez, M., and Scarisbrick, I.A. (2014). Differential expression of multiple kallikreins in a viral model of multiple sclerosis points to unique roles in the innate and adaptive immune response. Biol. Chem. 395, 1063–1073.10.1515/hsz-2014-0141Suche in Google Scholar PubMed PubMed Central

Paul, I., Bhattacharya, S., Chatterjee, A., and Ghosh, M.K. (2013). Current understanding on EGFR and Wnt/beta-catenin signaling in glioma and their possible crosstalk. Genes Cancer 4, 427–446.10.1177/1947601913503341Suche in Google Scholar PubMed PubMed Central

Pekny, M., Pekna, M., Messing, A., Steinhauser, C., Lee, J.M., Parpura, V., Hol, E.M., Sofroniew, M.V., and Verkhratsky, A. (2016). Astrocytes: a central element in neurological diseases. Acta Neuropathol. 131, 323–345.10.1007/s00401-015-1513-1Suche in Google Scholar PubMed

Prassas, I., Eissa, A., Poda, G., and Diamandis, E.P. (2015). Unleashing the therapeutic potential of human kallikrein-related serine proteases. Nat. Rev. Drug Discov. 14, 183–202.10.1038/nrd4534Suche in Google Scholar PubMed

Radulovic, M., Yoon, H., Larson, N., Wu, J., Linbo, R., Burda, J.E., Diamandis, E.P., Blaber, S.I., Blaber, M., Fehlings, M.G., et al. (2013). Kallikrein cascades in traumatic spinal cord injury: in vitro evidence for roles in axonopathy and neuron degeneration. J. Neuropathol. Exp. Neurol. 72, 1072–1089.10.1097/NEN.0000000000000007Suche in Google Scholar PubMed PubMed Central

Radulovic, M., Yoon, H., Wu, J., Mustafa, K., Fehlings, M.G., and Scarisbrick, I.A. (2015). Genetic targeting of protease activated receptor 2 reduces inflammatory astrogliosis and improves recovery of function after spinal cord injury. Neurobiol. Dis. 83, 75–89.10.1016/j.nbd.2015.08.021Suche in Google Scholar PubMed PubMed Central

Radulovic, M., Yoon, H., Wu, J., Mustafa, K., and Scarisbrick, I.A. (2016). Targeting the thrombin receptor modulates inflammation and astrogliosis to improve recovery after spinal cord injury. Neurobiol. Dis. 93, 226–242.10.1016/j.nbd.2016.04.010Suche in Google Scholar PubMed PubMed Central

Rajput, P.S., Lyden, P.D., Chen, B., Lamb, J.A., Pereira, B., Lamb, A., Zhao, L., Lei, I.F., and Bai, J. (2014). Protease activated receptor-1 mediates cytotoxicity during ischemia using in vivo and in vitro models. Neuroscience 281C, 229–240.10.1016/j.neuroscience.2014.09.038Suche in Google Scholar PubMed PubMed Central

Ramachandran, R., Eissa, A., Mihara, K., Oikonomopoulou, K., Saifeddine, M., Renaux, B., Diamandis, E., and Hollenberg, M.D. (2012). Proteinase-activated receptors (PARs): differential signalling by kallikrein-related peptidases KLK8 and KLK14. Biol. Chem. 393, 421–427.10.1515/hsz-2011-0251Suche in Google Scholar PubMed

Rohatgi, T., Henrich-Noack, P., Sedehizade, F., Goertler, M., Wallesch, C.W., Reymann, K.G., and Reiser, G. (2004). Transient focal ischemia in rat brain differentially regulates mRNA expression of protease-activated receptors 1 to 4. J. Neurosci. Res. 75, 273–279.10.1002/jnr.10847Suche in Google Scholar PubMed

Sandberg, C.J., Altschuler, G., Jeong, J., Stromme, K.K., Stangeland, B., Murrell, W., Grasmo-Wendler, U.H., Myklebost, O., Helseth, E., Vik-Mo, E.O., et al. (2013). Comparison of glioma stem cells to neural stem cells from the adult human brain identifies dysregulated Wnt- signaling and a fingerprint associated with clinical outcome. Exp. Cell Res. 319, 2230–2243.10.1016/j.yexcr.2013.06.004Suche in Google Scholar

Scarisbrick, I.A., Towner, M.D., and Isackson, P.J. (1996). Induction of serine proteases in the adult rat spinal cord following kainic acid administration. Soc. Neurosci. Abs. 22, 746.10.1016/0736-5748(96)80242-5Suche in Google Scholar

Scarisbrick, I.A., Towner, M.D., and Isackson, P. J. (1997). Nervous system specific expression of a novel serine protease: regulation in the adult rat spinal cord by excitotoxic injury. J. Neurosci. 17, 8156–8168.10.1523/JNEUROSCI.17-21-08156.1997Suche in Google Scholar

Scarisbrick, I.A., Asakura, K., Blaber, S., Blaber, M., Isackson, P.J., Beito, T., Rodriguez, M., and Windebank, A.J. (2000). Preferential expression of myelencephalon specific protease by oligodendrocytes of the adult rat spinal cord white matter. Glia 30, 219–230.10.1002/(SICI)1098-1136(200005)30:3<219::AID-GLIA2>3.0.CO;2-2Suche in Google Scholar

Scarisbrick, I.A. (2012). Kallikrein activity in the central nervous system. The Kallikreins. M. Schmitt, Sommerhoff, C., Fritz, H. and Magdolen, V. Berlin, De Gruyter Publishing: 349–372.Suche in Google Scholar

Scarisbrick, I.A. and Blaber, M. (2012). Kallikrein-related peptidase 6. In: Handbook of proteolytic enzymes. A.J. Barrett and N.D. Rawlings, eds. (London, UK: Elsevier), pp. 2780–2786.10.1016/B978-0-12-382219-2.00612-8Suche in Google Scholar

Scarisbrick, I.A., Blaber, S.I., Lucchinetti, C.F., Genain, C.P., Blaber, M., and Rodriguez, M. (2002). Activity of a newly identified serine protease in CNS demyelination. Brain 125, 1283–1296.10.1093/brain/awf142Suche in Google Scholar

Scarisbrick, I.A., Sabharwal, P., Cruz, H., Larsen, N., Vandell, A., Blaber, S.I., Ameenuddin, S., Papke, L.M., Fehlings, M.G., Reeves, R.K., et al. (2006). Dynamic role of kallikrein 6 in traumatic spinal cord injury. Eur. J. Neurosci 24, 1457–1469.10.1111/j.1460-9568.2006.05021.xSuche in Google Scholar

Scarisbrick, I.A., Epstein, B., Cloud, B.A., Yoon, H., Wu, J., Renner, D.N., Blaber, S. I., Blaber, M., Vandell, A.G., and Bryson, A.L. (2011). Functional role of kallikrein 6 in regulating immune cell survival. PLoS One 6, e18376.10.1371/journal.pone.0018376Suche in Google Scholar

Scarisbrick, I.A., Radulovic, M., Burda, J.E., Larson, N., Blaber, S.I., Giannini, C., Blaber, M., and Vandell, A.G. (2012a). Kallikrein 6 is a novel molecular trigger of reactive astrogliosis. Biol. Chem. 393, 355–367.10.1515/hsz-2011-0241Suche in Google Scholar

Scarisbrick, I.A., Yoon, H., Panos, M., Larson, N., Blaber, S.I., Blaber, M., and Rodriguez, M. (2012b). Kallikrein 6 regulates early CNS demyelination in a viral model of multiple sclerosis. Brain Pathol. 22, 709–722.10.1111/j.1750-3639.2012.00577.xSuche in Google Scholar

Schrader, C.H., Kolb, M., Zaoui, K., Flechtenmacher, C., Grabe, N., Weber, K.J., Hielscher, T., Plinkert, P.K., and Hess, J. (2015). Kallikrein-related peptidase 6 regulates epithelial-to-mesenchymal transition and serves as prognostic biomarker for head and neck squamous cell carcinoma patients. Mol. Cancer 14, 107.10.1186/s12943-015-0381-6Suche in Google Scholar PubMed PubMed Central

Shigetomi, E., Bowser, D.N., Sofroniew, M.V., and Khakh, B.S. (2008). Two forms of astrocyte calcium excitability have distinct effects on NMDA receptor-mediated slow inward currents in pyramidal neurons. J. Neurosci. 28, 6659–6663.10.1523/JNEUROSCI.1717-08.2008Suche in Google Scholar PubMed PubMed Central

Silver, J. and Miller, J.H. (2004). Regeneration beyond the glial scar. Nat. Rev. Neurosci. 5, 146–156.10.1038/nrn1326Suche in Google Scholar PubMed

Sotiropoulou, G. and Pampalakis, G. (2010). Kallikrein-related peptidases: bridges between immune functions and extracellular matrix degradation. Biol. Chem. 391, 321–331.10.1515/bc.2010.036Suche in Google Scholar

Spencer, B., Michael, S., Shen, J., Kosberg, K., Rockenstein, E., Patrick, C., Adame, A., and Masliah, E. (2013). Lentivirus mediated delivery of neurosin promotes clearance of wild-type alpha-synuclein and reduces the pathology in an alpha-synuclein model of LBD. Mol. Ther. 21, 31–41.10.1038/mt.2012.66Suche in Google Scholar PubMed PubMed Central

Spencer, B., Valera, E., Rockenstein, E., Trejo-Morales, M., Adame, A., and Masliah, E. (2015). A brain-targeted, modified neurosin (kallikrein-6) reduces alpha-synuclein accumulation in a mouse model of multiple system atrophy. Mol. Neurodegener 10, 48.10.1186/s13024-015-0043-6Suche in Google Scholar PubMed PubMed Central

Tatebe, H., Watanabe, Y., Kasai, T., Mizuno, T., Nakagawa, M., Tanaka, M., and Tokuda, T. (2010). Extracellular neurosin degrades α-synuclein in cultured cells. Neurosci. Res. 67, 341–346.10.1016/j.neures.2010.04.008Suche in Google Scholar PubMed

Terayama, R., Bando, Y., Takahashi, T., and Yoshida, S. (2004). Differential expression of neuropsin and protease M/neurosin in oligodendrocytes after injury to the spinal cord. Glia 48, 91–101.10.1002/glia.20058Suche in Google Scholar PubMed

Tong, X., Shigetomi, E., Looger, L.L., and Khakh, B.S. (2013). Genetically encoded calcium indicators and astrocyte calcium microdomains. Neuroscientist 19, 274–291.10.1177/1073858412468794Suche in Google Scholar PubMed

Uchida, A., Oka, Y., Aoyama, M., Suzuki, S., Yokoi, T., Katano, H., Mase, M., Tada, T., Asai, K., and Yamada, K. (2004). Expression of myelencephalon-specific protease in transient middle cerebral artery occlusion model of rat brain. Brain Res. Mol. Brain Res. 126, 129–136.10.1016/j.molbrainres.2004.04.009Suche in Google Scholar PubMed

Vandell, A.G., Larson, N., Laxmikanthan, G., Panos, M., Blaber, S.I., Blaber, M., and Scarisbrick, I.A. (2008). Protease activated receptor dependent and independent signaling by kallikreins 1 and 6 in CNS neuron and astroglial cell lines. J. Neurochem. 107, 855–870.10.1111/j.1471-4159.2008.05658.xSuche in Google Scholar

Verkhratsky, A., Orkand, R.K., and Kettenmann, H. (1998). Glial calcium: homeostasis and signaling function. Physiol. Rev. 78, 99–141.10.1152/physrev.1998.78.1.99Suche in Google Scholar

Wang, H., Ubl, J.J., and Reiser, G. (2002). Four subtypes of protease-activated receptors, co-expressed in rat astrocytes, evoke different physiological signaling. Glia 37, 53–63.10.1002/glia.10012Suche in Google Scholar

Wang, H., Wen, S., Bunnett, N.W., Leduc, R., Hollenberg, M.D., and MacNaughton, W.K. (2008). Proteinase-activated receptor-2 induces cyclooxygenase-2 expression through β-catenin and cyclic AMP-response element-binding protein. J. Biol. Chem. 283, 809–815.10.1074/jbc.M703021200Suche in Google Scholar

Yamashiro, K., Tsuruoka, N., Kodama, S., Tsujimoto, M., Yamamura, Y., Tanaka, T., Nakazato, H., and Yamaguchi, N. (1997). Molecular cloning of a novel trypsin-like serine protease (neurosin) preferentially expressed in brain. Biochim. Biophys. Acta 1350, 11–14.10.1016/S0167-4781(96)00187-XSuche in Google Scholar

Yoon, H., Radulovic, M., Wu, J., Blaber, S.I., Blaber, M., Fehlings, M.G., and Scarisbrick, I.A. (2013). Kallikrein 6 signals through PAR1 and PAR2 to promote neuron injury and exacerbate glutamate neurotoxicity. J. Neurochem. 127, 283–298.10.1111/jnc.12293Suche in Google Scholar

Yoon, H., Walters, G., Paulsen, A.R., and Scarisbrick, I.A. (2017). Astrocyte heterogeneity across the brain and spinal cord occurs developmentally, in adulthood and in response to demyelination. PLoS One 12, e0180697.10.1371/journal.pone.0180697Suche in Google Scholar

Yuan, Y.M. and He, C. (2013). The glial scar in spinal cord injury and repair. Neurosci Bull 29, 421–435.10.1007/s12264-013-1358-3Suche in Google Scholar

Zarghooni, M., Soosaipillai, A., Grass, L., Scorilas, A., Mirazimi, N., and Diamandis, E. P. (2002). Decreased concentration of human kallikrein 6 in brain extracts of Alzheimer’s disease patients. Clin. Biochem. 35, 225–231.10.1016/S0009-9120(02)00292-8Suche in Google Scholar

Received: 2018-01-15
Accepted: 2018-03-26
Published Online: 2018-03-31
Published in Print: 2018-09-25

©2018 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Highlight: The 7th International Symposium on Kallikreins and Kallikrein-Related Peptidases
  3. Obituary
  4. Manfred Schmitt (1947–2018)
  5. Functional interrelationships between the kallikrein-related peptidases family and the classical kinin system in the human neutrophil
  6. Overview of tissue kallikrein and kallikrein-related peptidases in breast cancer
  7. Kallikrein-related peptidases in lung diseases
  8. The miRNA-kallikrein interaction: a mosaic of epigenetic regulation in cancer
  9. Mining human cancer datasets for kallikrein expression in cancer: the ‘KLK-CANMAP’ Shiny web tool
  10. Specificity profiling of human trypsin-isoenzymes
  11. Activation and activity of glycosylated KLKs 3, 4 and 11
  12. Microenvironment proteinases, proteinase-activated receptor regulation, cancer and inflammation
  13. Kallikrein-related peptidase 6 orchestrates astrocyte form and function through proteinase activated receptor-dependent mechanisms
  14. Kallikrein-related peptidase 5 and seasonal influenza viruses, limitations of the experimental models for activating proteases
  15. Novel splice variants of the human kallikrein-related peptidases 11 (KLK11) and 12 (KLK12), unraveled by next-generation sequencing technology
  16. Insights into the activity control of the kallikrein-related peptidase 6: small-molecule modulators and allosterism
  17. Kallikrein-related peptidase 14 is the second KLK protease targeted by the serpin vaspin
  18. Profiling system for skin kallikrein proteolysis applied in gene-deficient mouse models
  19. Evidence that cell surface localization of serine protease activity facilitates cleavage of the protease activated receptor CDCP1
  20. Kallikrein-related peptidase 7 overexpression in melanoma cells modulates cell adhesion leading to a malignant phenotype
  21. KLK5, a novel potential suppressor of vaginal carcinogenesis
Heruntergeladen am 24.10.2025 von https://www.degruyterbrill.com/document/doi/10.1515/hsz-2018-0122/html
Button zum nach oben scrollen