1. Noorbakhsh F, Vergnolle N, Hollenberg MD, Power C. Proteinase-activated receptors in the nervous system. Nat Rev Neurosci. 2003;4(12): 981-90. [DOI:10.1038/nrn1255]

2. Zhao P, Metcalf M, Bunnett NW. Biased signaling of protease-activatedreceptors. Front Endocrinol (Lausanne). 2014; 5: 67. doi: 10.3389/fendo.2014.00067. [DOI:10.3389/fendo.2014.00067]

3. Ramachandran R, Noorbakhsh F, Defea K, Hollenberg MD. Targeting proteinase-activated receptors: therapeutic potential and challenges. Nat Rev Drug Discov. 2012;11(1): 69-86. [DOI:10.1038/nrd3615]

4. Noorbakhsh F, Tsutsui S, Vergnolle N, Boven LA, Shariat N, Vodjgani M, et al. Proteinase-activated receptor 2 modulates neuroinflammation in experimental autoimmune encephalomyelitis and multiple sclerosis. J Exp Med. 2006; 203(2): 425-35. [DOI:10.1084/jem.20052148]

5. Vu TK, Hung DT, Wheaton VI, Coughlin SR. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell. 1991; 64(6): 1057-68. [DOI:10.1016/0092-8674(91)90261-V]

6. Rasmussen UB, Vouret-Craviari V, Jallat S, Schlesinger Y, Pages G, Pavirani A, et al. cDNA cloning and expression of a hamster alpha-thrombin receptor coupled to Ca2+ mobilization. FEBS Lett. 1991; 288(1-2): 123-8. [DOI:10.1016/0014-5793(91)81017-3]

7. Nystedt S, Emilsson K, Wahlestedt C, Sundelin J. Molecular cloning of a potential proteinase activated receptor. Proc Natl Acad Sci U S A. 1994; 91(20): 9208-12. [DOI:10.1073/pnas.91.20.9208]

8. Bohm SK, Kong W, Bromme D, Smeekens SP, Anderson DC, Connolly A, et al. Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2. Biochem J. 1996; 314(3): 1009-16. [DOI:10.1042/bj3141009]

9. Adams MN, Ramachandran R, Yau MK, Suen JY, Fairlie DP, Hollenberg MD, et al. Structure, function and pathophysiology of protease activated receptors. Pharmacol Ther. 2011; 130(3): 248-82. [DOI:10.1016/j.pharmthera.2011.01.003]

10. Nakanishi-Matsui M, Zheng YW, Sulciner DJ, Weiss EJ, Ludeman MJ, Coughlin SR. PAR3 is a cofactor for PAR4 activation by thrombin. Nature.2000; 404(6778): 609-13. [DOI:10.1038/35007085]

11. McLaughlin JN, Patterson MM, Malik AB. Protease-activated receptor-3 (PAR3) regulates PAR1 signaling by receptor dimerization. Proc Natl Acad Sci U S A. 2007; 104(13): 5662-7. [DOI:10.1073/pnas.0700763104]

12. Defea K. Beta-arrestins and heterotrimeric G-proteins: collaborators and competitors in signal transduction. Br J Pharmacol. 2008; 153(1): S298-309.

13. Dulon S, Cande C, Bunnett NW, Hollenberg MD, Chignard M, Pidard D. Proteinase-activated receptor-2 and human lung epithelial cells: disarming by neutrophil serine proteinases. Am J Respir Cell Mol Biol. 2003; 28(3): 339-46. [DOI:10.1165/rcmb.4908]

14. Renesto P, Si-Tahar M, Moniatte M, Balloy V, Van Dorsselaer A, Pidard D, et al. Specific inhibition of thrombin-induced cell activation by the neutrophil proteinases elastase, cathepsin G, and proteinase 3: evidence for distinct cleavage sites within the amino terminal domain of the thrombin receptor. Blood. 1997; 89(6): 1944-53.

15. Ramachandran R, Mihara K, Chung H, Renaux B, Lau CS, Muruve DA, et al. Neutrophil elastase acts as a biased agonist for proteinase-activated receptor-2 (PAR2). J Biol Chem. 2011; 286(28): 24638-48. [DOI:10.1074/jbc.M110.201988]

16. Scarborough RM, Naughton MA, Teng W, Hung DT, Rose J, Vu TK, et al. Tethered ligand agonist peptides. Structural requirements for thrombin receptor activation reveal mechanism of proteolytic unmasking of agonist function. J Biol Chem. 1992;267(19): 13146-9.

17. Hollenberg MD, Saifeddine M, al-Ani B, Kawabata A. Proteinase-activated receptors: structural requirements for activity, receptor cross-reactivity, and receptor selectivity of receptor-activating peptides. Can J Physiol Pharmacol. 1997; 75(7): 832-41. [DOI:10.1139/y97-110]

18. Striggow F, Riek-Burchardt M, Kiesel A, Schmidt W, Henrich-Noack P, Breder J, et al. Four different types of protease-activated receptors are widely expressed in the brain and are up-regulated in hippocampus by severe ischemia. Eur J Neurosci. 2001; 14(4): 595-608. [DOI:10.1046/j.0953-816x.2001.01676.x]

19. Henrich-Noack P, Riek-Burchardt M, Baldauf K, Reiser G, Reymann KG. Focal ischemia induces expressionof protease-activated receptor1 (PAR1) and PAR3 on microglia and enhances PAR4 labeling in the penumbra. Brain res. 2006; 1070(1): 232-41. [DOI:10.1016/j.brainres.2005.10.100]

20. Suo Z, Wu M, Citron BA, Gao C, Festoff BW. Persistent protease-activated receptor 4 signaling mediates thrombin-induced microglial activation. J Biol Chem. 2003; 278(33): 31177-83. [DOI:10.1074/jbc.M302137200]

21. Wang H, Ubl JJ, Reiser G. Four subtypes of protease-activated receptors, co-expressed in rat astrocytes, evoke different physiological signaling. Glia. 2002; 37(1): 53-63. [DOI:10.1002/glia.10012]

22. Scarisbrick IA, Isackson PJ, Ciric B, Windebank AJ, Rodriguez M. MSP, a trypsin-like serine protease, is abundantly expressed in the human nervous system. J Comp Neurol. 2001; 431(3): 347-61. https://doi.org/10.1002/1096-9861(20010312)431:3<347::AID-CNE1075>3.0.CO;2-K [DOI:10.1002/1096-9861(20010312)431:33.0.CO;2-K]

23. Bernett MJ, Blaber SI, Scarisbrick IA, Dhanarajan P, Thompson SM, Blaber M. 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. 2002; 277(27): 24562-70. [DOI:10.1074/jbc.M202392200]

24. Sokolova E, Reiser G. Prothrombin/thrombin and the thrombin receptors PAR-1 and PAR-4 inthe brain: localization, expression and participation in neurodegenerative diseases. Thromb Haemost. 2008; 100(4): 576-81. [DOI:10.1160/TH08-03-0131]

25. Yoshida S, Shiosaka S. Plasticity-related serine proteases in the brain (review). Int J Mol Med. 1999; 3(4): 405-9. [DOI:10.3892/ijmm.3.4.405]

26. Turgeon VL, Houenou LJ. The role of thrombin-like (serine) proteases in the development, plasticity and pathology of the nervous system. Brain Res Brain Res Rev. 1997; 25(1): 85-95. [DOI:10.1016/S0165-0173(97)00015-5]

27. Deschepper CF, Bigornia V, Berens ME, Lapointe MC. Production of thrombin and antithrombin III by brain and astroglial cell cultures. Molecular Brain Research. 1991; 11(3-4): 355-8 [DOI:10.1016/0169-328X(91)90045-Y]

28. Dihanich M, Kaser M, Reinhard E, Cunningham D, Monard D. Prothrombin mRNA is expressed by cells of the nervous system. Neuron. 1991; 6(4): 575-81. [DOI:10.1016/0896-6273(91)90060-D]

29. Shikamoto Y, Morita T. Expression of factor X in boththe rat brain and cells of the central nervous system. FEBS lett. 1999; 463(3): 387-9. [DOI:10.1016/S0014-5793(99)01657-9]

30. Theoharides TC. Mast cells: the immune gate to the brain. Life Sci. 1990; 46(9): 607-17. [DOI:10.1016/0024-3205(90)90129-F]

31. Stead RH, Tomioka M, Quinonez G, Simon GT, Felten SY, Bienenstock J. Intestinal mucosal mast cells in normal and nematode-infected rat intestines are in intimate contact with peptidergic nerves. Proc Natl Acad Sci U S A. 1987; 84(9): 2975-9. [DOI:10.1073/pnas.84.9.2975]

32. Luo W, Wang Y, Reiser G. Protease-activated receptors in the brain: receptor expression, activation, and functions in neurodegeneration and neuroprotection. Brain Res Rev. 2007; 56(2): 331-45. [DOI:10.1016/j.brainresrev.2007.08.002]

33. Tanaka M, Yoneyama M, Shiba T, Yamaguchi T, Ogita K. Protease-activated receptor-1 negatively regulates proliferation of neural stem/progenitor cells derived from the hippocampal dentate gyrus of the adult mouse. J Pharmacol Sci. 2016; 131(3): 162-71. [DOI:10.1016/j.jphs.2016.05.005]

34. Beecher KL, Andersen TT, Fenton JW, Festoff BW. Thrombin receptor peptides induce shape change in neonatal murine astrocytes in culture. J Neurosci Res. 1994; 37(1)108-15 [DOI:10.1002/jnr.490370115]

35. Junge CE, Sugawara T, Mannaioni G, Alagarsamy S, Conn PJ, Brat DJ, et al. The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebralischemia. Proc Natl Acad Sci U S A. 2003; 100(22): 13019-24. [DOI:10.1073/pnas.2235594100]

36. Hamill CE, Mannaioni G, Lyuboslavsky P, Sastre AA, Traynelis SF. Protease-activated receptor 1-dependent neuronal damage involves NMDA receptor function. Exp Neurol. 2009; 217(1): 136-46. [DOI:10.1016/j.expneurol.2009.01.023]

37. Zhen X, Ng ES, Lam FF. Suppression of ischaemia-induced injuries in ratbrain by protease-activated receptor-1 (PAR-1) activating peptide. Eur J Pharmacol. 2016; 786: 36-46. [DOI:10.1016/j.ejphar.2016.05.035]

38. Xue M, Hollenberg MD, Demchuk A, Yong VW. Relative importance of proteinase-activated receptor-1 versusmatrixmetalloproteinases in intracerebral hemorrhage-mediated neurotoxicity in mice. Stroke. 2009; 40(6): 2199-204. [DOI:10.1161/STROKEAHA.108.540393]

39. Acharjee S, Zhu Y, Maingat F, Pardo C, Ballanyi K, Hollenberg MD, et al. Proteinase-activated receptor-1 mediates dorsal root ganglion neuronal degeneration in HIV/AIDS. Brain. 2011; 134(11): 3209-21. [DOI:10.1093/brain/awr242]

40. Boven LA, Vergnolle N, Henry SD, Silva C, Imai Y, Holden J, et al. Up-regulation of proteinase-activated receptor 1 expression in astrocytes during HIV encephalitis. J Immunol. 2003; 170(5): 2638-46. [DOI:10.4049/jimmunol.170.5.2638]

41. Lee EJ, Woo MS, Moon PG, Baek MC, Choi IY, Kim WK, et al. Alpha-synuclein activates microglia by inducing the expressions of matrix metalloproteinases and the subsequent activation of protease-activated receptor-1. J Immunol. 2010; 185(1): 615-23. [DOI:10.4049/jimmunol.0903480]

42. Hamill CE, Caudle WM, Richardson JR, Yuan H, Pennell KD, Greene JG, et al. Exacerbation of dopaminergic terminal damage in a mouse model of Parkinson's disease by the G-protein-coupled receptor protease-activated receptor 1. Mol Pharmacol. 2007; 72(3): 653-64. [DOI:10.1124/mol.107.038158]

43. Nicole O, Goldshmidt A, Hamill CE, Sorensen SD, Sastre A, Lyuboslavsky P, et al. Activation of protease-activated receptor-1 triggers astrogliosis after brain injury. J Neurosci. 2005; 25(17): 4319-29. [DOI:10.1523/JNEUROSCI.5200-04.2005]

44. Gan J, Greenwood SM, Cobb SR, Bushell TJ. Indirect modulation of neuronal excitability and synaptic transmission in the hippocampus by activation of proteinase-activated receptor-2. BJP. 2011; 163(5): 984-94. [DOI:10.1111/j.1476-5381.2011.01293.x]

45. Lohman RJ, O'Brien TJ, Cocks TM. Protease-activated receptor-2 regulates trypsin expression in the brain and protects against seizuresandepileptogenesis. Neurobiol Dis. 2008; 30(1): 84-93. [DOI:10.1016/j.nbd.2007.12.010]

46. Lohman RJ, Jones NC, O'Brien TJ, Cocks TM. A regulatory role for protease-activated receptor-2 in motivational learning in rats. Neurobiol Learn Mem. 2009; 92(3): 301-9. [DOI:10.1016/j.nlm.2009.03.010]

47. Afkhami-Goli A, Noorbakhsh F, Keller AJ, Vergnolle N, Westaway D, Jhamandas JH, et al. Proteinase-activated receptor-2 exerts protective and pathogenic cell type-specific effects in Alzheimer's disease. J Immunol. 2007; 179(8): 5493-503. [DOI:10.4049/jimmunol.179.8.5493]

48. 48 Noorbakhsh F, Vergnolle N, McArthur JC, Silva C, Vodjgani M, Andrade-Gordon P, et al. Proteinase-activated receptor-2 induction by neuroinflammation prevents neuronal deathduring HIV infection. J Immunol. 2005; 174(11): 7320-9. [DOI:10.4049/jimmunol.174.11.7320]

49. Jin G, Hayashi T, Kawagoe J, Takizawa T, Nagata T, Nagano I, et al. Deficiency of PAR-2 gene increases acute focal ischemic brain injury. Journal of cerebral blood flow andmetabolism: J Cereb Blood Flow Metab. 2005; 25(3): 302-13. [DOI:10.1038/sj.jcbfm.9600021]

50. Bar-Shavit R, Maoz M, Kancharla A, Jaber M, Agranovich D, Grisaru-Granovsky S, et al. Protease-activated receptors (PARs) in cancer: Novel biased signaling and targets for therapy. Methods Cell Biol. 2016; 132: 341-58. [DOI:10.1016/bs.mcb.2015.11.006]

51. Mao Y, Zhang M, Tuma RF, Kunapuli SP. Deficiency of PAR4 attenuates cerebral ischemia/reperfusion injury in mice. J Cereb Blood Flow Metab. 2010; 30(5): 1044-52. [DOI:10.1038/jcbfm.2009.283]

52. Rothmeier AS, Ruf W. Protease-activated receptor 2 signaling in inflammation. Semin Immunopathol. 2012; 34(1): 133-49. [DOI:10.1007/s00281-011-0289-1]

53. Steinhoff M, Vergnolle N, Young SH, Tognetto M, Amadesi S, Ennes HS, et al. Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med. 2000; 6(2): 151-8. [DOI:10.1038/72247]

54. Chen K, Zhang ZF, Liao MF, Yao WL, Wang J, Wang XR. Blocking PAR2 attenuates oxaliplatin-induced neuropathic pain via TRPV1 and releases of substance P and CGRP in superficial dorsal horn of spinal cord. J Neurol Sci. 2015; 352(1-2): 62-7. [DOI:10.1016/j.jns.2015.03.029]

55. Asfaha S, Brussee V, Chapman K, Zochodne DW, Vergnolle N. Proteinase-activated receptor-1 agonists attenuate nociception in response to noxious stimuli. Br J Pharmacol. 2002; 135(5): 1101-6. [DOI:10.1038/sj.bjp.0704568]

56. Bao Y, Gao Y, Yang L, Kong X, Zheng H, Hou W, et al. New insights into protease-activated receptor 4 signaling pathways in the pathogenesis of inflammation and neuropathic pain: a literature review. Channels. 2015; 9(1): 5-13. [DOI:10.4161/19336950.2014.995001]