Prothrombin kringle-2: A potential inflammatory pathogen in the parkinsonian dopaminergic system

Experimental Neurobiology

Volumn 25, Issue 4, 2016, Pages 147-155

  Leem, Eunju ^a   Jeong, Kyoung Hoon ^a   Won, So Yoon ^b   Shin, Won Ho ^c   Kim, Sang Ryong ^a  

^a Kyungpook National University   (South Korea)

^b Chungbuk National University College of Medicine   (South Korea)

^c Korea Institute of Toxicology   (South Korea)

Author keywords

Microglia; Parkinson's disease; Prothrombin kringle 2; Toll like receptor 4

Indexed keywords

EID: 84995582124     PISSN: 12262560     EISSN: 20938144     Source Type: Journal    
DOI: 10.5607/en.2016.25.4.147     Document Type: Article

References (71)

1. Kim SR, Kareva T, Yarygina O, Kholodilov N, Burke RE (2012) AAV transduction of dopamine neurons with constitutively active Rheb protects from neurodegeneration and mediates axon regrowth. Mol Ther 20:275-286.
2. Nam JH, Leem E, Jeon MT, Jeong KH, Park JW, Jung UJ, Kholodilov N, Burke RE, Jin BK, Kim SR (2015) Induction of GDNF and BDNF by hRheb(S16H) transduction of SNpc neurons: neuroprotective mechanisms of hRheb(S16H) in a model of Parkinson's disease. Mol Neurobiol 51:487-499.
3. Shin WH, Jeon MT, Leem E, Won SY, Jeong KH, Park SJ, McLean C, Lee SJ, Jin BK, Jung UJ, Kim SR (2015) Induction of microglial toll-like receptor 4 by prothrombin kringle-2: a potential pathogenic mechanism in Parkinson's disease. Sci Rep 5:14764.
4. Hirsch EC, Hunot S (2009) Neuroinflammation in Parkinson's disease: a target for neuroprotection? Lancet Neurol 8:382-397.
5. Kim SR, Chung ES, Bok E, Baik HH, Chung YC, Won SY, Joe E, Kim TH, Kim SS, Jin MY, Choi SH, Jin BK (2010) Prothrombin kringle-2 induces death of mesencephalic dopaminergic neurons in vivo and in vitro via microglial activation. J Neurosci Res 88:1537-1548.
6. Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783-801.
7. Kagan JC, Medzhitov R (2006) Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling. Cell 125:943-955.
8. Jin JJ, Kim HD, Maxwell JA, Li L, Fukuchi K (2008) Tolllike receptor 4-dependent upregulation of cytokines in a transgenic mouse model of Alzheimer's disease. J Neuroinflammation 5:23.
9. Song M, Jin J, Lim JE, Kou J, Pattanayak A, Rehman JA, Kim HD, Tahara K, Lalonde R, Fukuchi K (2011) TLR4 mutation reduces microglial activation, increases Aß deposits and exacerbates cognitive deficits in a mouse model of Alzheimer's disease. J Neuroinflammation 8:92.
10. Fellner L, Irschick R, Schanda K, Reindl M, Klimaschewski L, Poewe W, Wenning GK, Stefanova N (2013) Toll-like receptor 4 is required for alpha-synuclein dependent activation of microglia and astroglia. Glia 61:349-360.
11. Stefanova N, Reindl M, Neumann M, Kahle PJ, Poewe W, Wenning GK (2007) Microglial activation mediates neurodegeneration related to oligodendroglial alphasynucleinopathy: implications for multiple system atrophy. Mov Disord 22:2196-2203.
12. Dauer W, Przedborski S (2003) Parkinson's disease: mechanisms and models. Neuron 39:889-909.
13. Kalia LV, Lang AE (2015) Parkinson's disease. Lancet 386:896-912.
14. Katzenschlager R, Lees AJ (2002) Treatment of Parkinson's disease: levodopa as the first choice. J Neurol 249 Suppl 2:II19-II24.
15. Thanvi BR, Lo TC (2004) Long term motor complications of levodopa: clinical features, mechanisms, and management strategies. Postgrad Med J 80:452-458.
16. Winklhofer KF, Haass C (2010) Mitochondrial dysfunction in Parkinson's disease. Biochim Biophys Acta 1802:29-44.
17. Exner N, Lutz AK, Haass C, Winklhofer KF (2012) Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences. EMBO J 31:3038-3062.
18. Cui K, Luo X, Xu K, Ven Murthy MR (2004) Role of oxidative stress in neurodegeneration: recent developments in assay methods for oxidative stress and nutraceutical antioxidants. Prog Neuropsychopharmacol Biol Psychiatry 28:771-799.
19. Wang Q, Liu Y, Zhou J (2015) Neuroinflammation in Parkinson's disease and its potential as therapeutic target. Transl Neurodegener 4:19.
20. Imamura K, Hishikawa N, Sawada M, Nagatsu T, Yoshida M, Hashizume Y (2003) Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson's disease brains. Acta Neuropathol 106:518-526.
21. Ouchi Y, Yoshikawa E, Sekine Y, Futatsubashi M, Kanno T, Ogusu T, Torizuka T (2005) Microglial activation and dopamine terminal loss in early Parkinson's disease. Ann Neurol 57:168-175.
22. Hanisch UK (2002) Microglia as a source and target of cytokines. Glia 40:140-155.
23. Gomes-Leal W (2012) Microglial physiopathology: how to explain the dual role of microglia after acute neural disorders? Brain Behav 2:345-356.
24. Frank-Cannon TC, Alto LT, McAlpine FE, Tansey MG (2009) Does neuroinflammation fan the flame in neurodegenerative diseases? Mol Neurodegener 4:47.
25. Kamata H, Hirata H (1999) Redox regulation of cellular signalling. Cell Signal 11:1-14.
26. Haslund-Vinding J, McBean G, Jaquet V, Vilhardt F (2016) NADPH oxidases in microglia oxidant production: activating receptors, pharmacology, and association with disease. Br J Pharmacol (in presss).
27. Miller RL, James-Kracke M, Sun GY, Sun AY (2009) Oxidative and inflammatory pathways in Parkinson's disease. Neurochem Res 34:55-65.
28. Wu DC, Teismann P, Tieu K, Vila M, Jackson-Lewis V, Ischiropoulos H, Przedborski S (2003) NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine model of Parkinson's disease. Proc Natl Acad Sci U S A 100:6145-6150.
29. Bové J, Perier C (2012) Neurotoxin-based models of Parkinson's disease. Neuroscience 211:51-76.
30. Wu DC, Jackson-Lewis V, Vila M, Tieu K, Teismann P, Vadseth C, Choi DK, Ischiropoulos H, Przedborski S (2002) Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine mouse model of Parkinson disease. J Neurosci 22:1763-1771.
31. Czlonkowska A, Kohutnicka M, Kurkowska-Jastrzebska I, Czlonkowski A (1996) Microglial reaction in MPTP (1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine) induced Parkinson's disease mice model. Neurodegeneration 5:137-143.
32. Cicchetti F, Brownell AL, Williams K, Chen YI, Livni E, Isacson O (2002) Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging. Eur J Neurosci 15:991-998.
33. Mosley RL, Benner EJ, Kadiu I, Thomas M, Boska MD, Hasan K, Laurie C, Gendelman HE (2006) Neuroinflammation, oxidative stress and the pathogenesis of Parkinson's disease. Clin Neurosci Res 6:261-281.
34. Mogi M, Harada M, Riederer P, Narabayashi H, Fujita K, Nagatsu T (1994) Tumor necrosis factor-alpha (TNF-a) increases both in the brain and in the cerebrospinal fluid from Parkinsonian patients. Neurosci Lett 165:208-210.
35. Kim HD, Jeong KH, Jung UJ, Kim SR (2016) Myricitrin ameliorates 6-hydroxydopamine-induced dopaminergic neuronal loss in the substantia nigra of mouse brain. J Med Food 19:374-382.
36. Rodriguez-Pallares J, Parga JA, Muñoz A, Rey P, Guerra MJ, Labandeira-Garcia JL (2007) Mechanism of 6-hydroxydopamine neurotoxicity: the role of NADPH oxidase and microglial activation in 6-hydroxydopamineinduced degeneration of dopaminergic neurons. J Neurochem 103:145-156.
37. Hernandes MS, Santos GD, Café-Mendes CC, Lima LS, Scavone C, Munhoz CD, Britto LR (2013) Microglial cells are involved in the susceptibility of NADPH oxidase knockout mice to 6-hydroxy-dopamine-induced neurodegeneration. PLoS One 8:e75532.
38. Gao HM, Hong JS, Zhang W, Liu B (2002) Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 22:782-790.
39. Gao HM, Liu B, Hong JS (2003) Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 23:6181-6187.
40. Molteni M, Gemma S, Rossetti C (2016) The role of toll-like receptor 4 in infectious and noninfectious inflammation. Mediators Inflamm 2016:6978936.
41. Takeda K, Akira S (2005) Toll-like receptors in innate immunity. Int Immunol 17:1-14.
42. Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4:499-511.
43. Olson JK, Miller SD (2004) Microglia initiate central nervous system innate and adaptive immune responses through multiple TLRs. J Immunol 173:3916-3924.
44. Lehnardt S, Massillon L, Follett P, Jensen FE, Ratan R, Rosenberg PA, Volpe JJ, Vartanian T (2003) Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway. Proc Natl Acad Sci U S A 100:8514-8519.
45. Ahmad A, Crupi R, Campolo M, Genovese T, Esposito E, Cuzzocrea S (2013) Absence of TLR4 reduces neurovascular unit and secondary inflammatory process after traumatic brain injury in mice. PLoS One 8:e57208.
46. Caso JR, Pradillo JM, Hurtado O, Lorenzo P, Moro MA, Lizasoain I (2007) Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke. Circulation 115:1599-1608.
47. Kerfoot SM, Long EM, Hickey MJ, Andonegui G, Lapointe BM, Zanardo RC, Bonder C, James WG, Robbins SM, Kubes P (2004) TLR4 contributes to disease-inducing mechanisms resulting in central nervous system autoimmune disease. J Immunol 173:7070-7077.
48. Walter S, Letiembre M, Liu Y, Heine H, Penke B, Hao W, Bode B, Manietta N, Walter J, Schulz-Schuffer W, Fassbender K (2007) Role of the toll-like receptor 4 in neuroinflammation in Alzheimer's disease. Cell Physiol Biochem 20:947-956.
49. Gambuzza ME, Sofo V, Salmeri FM, Soraci L, Marino S, Bramanti P (2014) Toll-like receptors in Alzheimer's disease: a therapeutic perspective. CNS Neurol Disord Drug Targets 13:1542-1558.
50. Noelker C, Morel L, Lescot T, Osterloh A, Alvarez-Fischer D, Breloer M, Henze C, Depboylu C, Skrzydelski D, Michel PP, Dodel RC, Lu L, Hirsch EC, Hunot S, Hartmann A (2013) Toll like receptor 4 mediates cell death in a mouse MPTP model of Parkinson disease. Sci Rep 3:1393.
51. Park HS, Jung HY, Park EY, Kim J, Lee WJ, Bae YS (2004) Cutting edge: direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NFkappa B. J Immunol 173:3589-3593.
52. Dihanich M, Kaser M, Reinhard E, Cunningham D, Monard D (1991) Prothrombin mRNA is expressed by cells of the nervous system. Neuron 6:575-581.
53. Mann KG (1976) Prothrombin. Methods Enzymol 45:123-156.
54. Taneda H, Andoh K, Nishioka J, Takeya H, Suzuki K (1994) Blood coagulation factor Xa interacts with a linear sequence of the kringle 2 domain of prothrombin. J Biochem 116:589-597.
55. Shikamoto Y, Morita T (1999) Expression of factor X in both the rat brain and cells of the central nervous system. FEBS Lett 463:387-389.
56. Lee TH, Rhim T, Kim SS (1998) Prothrombin kringle-2 domain has a growth inhibitory activity against basic fibroblast growth factor-stimulated capillary endothelial cells. J Biol Chem 273:28805-28812.
57. Rhim T Y, Park CS, Kim E, Kim SS (1998) Human prothrombin fragment 1 and 2 inhibit bFGF-induced BCE cell growth. Biochem Biophys Res Commun 252:513-516.
58. Kim TH, Oh S, Kim SS (2005) Recombinant human prothrombin kringle-2 induces bovine capillary endothelial cell cycle arrest at G0-G1 phase through inhibition of cyclin D1/CDK4 complex: modulation of reactive oxygen species generation and up-regulation of cyclin-dependent kinase inhibitors. Angiogenesis 8:307-314.
59. Dasgupta SK, Thiagarajan P (2007) Inhibition of thrombin activity by prothrombin activation fragment 1.2. J Thromb Thrombolysis 24:157-162.
60. Kim TH, Ahn S, Kim J, Kim I, Yang MZ, Lee JE, Kim SS (2006) Recombinant human prothrombin kringle-2 inhibits B16F10 melanoma metastasis through inhibition of neovascularization and reduction of matrix metalloproteinase expression. Clin Exp Metastasis 23:391-399.
61. Ishida Y, Nagai A, Kobayashi S, Kim SU (2006) Upregulation of protease-activated receptor-1 in astrocytes in Parkinson disease: astrocyte-mediated neuroprotection through increased levels of glutathione peroxidase. J Neuropathol Exp Neurol 65:66-77.
62. Berzin TM, Zipser BD, Rafii MS, Kuo-Leblanc V, Yancopoulos GD, Glass DJ, Fallon JR, Stopa EG (2000) Agrin and microvascular damage in Alzheimer's disease. Neurobiol Aging 21:349-355.
63. Sokolova E, Reiser G (2008) Prothrombin/thrombin and the thrombin receptors PAR-1 and PAR-4 in the brain: localization, expression and participation in neurodegenerative diseases. Thromb Haemost 100:576-581.
64. Won SY, Choi SH, Jin BK (2009) Prothrombin kringle-2-induced oxidative stress contributes to the death of cortical neurons in vivo and in vitro: role of microglial NADPH oxidase. J Neuroimmunol 214:83-92.
65. Ryu J, Min KJ, Rhim TY, Kim TH, Pyo H, Jin B, Kim SU, Jou I, Kim SS, Joe EH (2002) Prothrombin kringle-2 activates cultured rat brain microglia. J Immunol 168:5805-5810.
66. Ros-Bernal F, Hunot S, Herrero MT, Parnadeau S, Corvol JC, Lu L, Alvarez-Fischer D, Carrillo-de Sauvage MA, Saurini F, Coussieu C, Kinugawa K, Prigent A, Höglinger G, Hamon M, Tronche F, Hirsch EC, Vyas S (2011) Microglial glucocorticoid receptors play a pivotal role in regulating dopaminergic neurodegeneration in Parkinsonism. Proc Natl Acad Sci U S A 108:6632-6637.
67. Choi SH, Lee DY, Chung ES, Hong YB, Kim SU, Jin BK (2005) Inhibition of thrombin-induced microglial activation and NADPH oxidase by minocycline protects dopaminergic neurons in the substantia nigra in vivo. J Neurochem 95:1755-1765.
68. Noble W, Garwood C, Stephenson J, Kinsey AM, Hanger DP, Anderton BH (2009) Minocycline reduces the development of abnormal tau species in models of Alzheimer's disease. FASEB J 23:739-750.
69. Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, Bian J, Guo L, Farrell LA, Hersch SM, Hobbs W, Vonsattel JP, Cha JH, Friedlander RM (2000) Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med 6:797-801.
70. Arvin KL, Han BH, Du Y, Lin SZ, Paul SM, Holtzman DM (2002) Minocycline markedly protects the neonatal brain against hypoxic-ischemic injury. Ann Neurol 52:54-61.
71. Sanchez Mejia RO, Ona VO, Li M, Friedlander RM (2001) Minocycline reduces traumatic brain injury-mediated caspase-1 activation, tissue damage, and neurological dysfunction. Neurosurgery 48:1393-1399.