Tissue plasminogen activator in central nervous system physiology and pathology

Summary

Although conventionally associated with fibrin clot degradation, recent work has uncovered new functions for the tissue plasminogen activator (tPA)/plasminogen cascade in central nervous system physiology and pathology. This extracellular proteolytic cascade has been shown to have roles in learning and memory, stress, neuronal degeneration, addiction and Alzheimer’s disease. The current review considers the different ways tPA functions in the brain.

Keywords

Tissue-type plasminogen activator - plasminogen - central nervous system - LTP - excitotoxicity

• References

• 1 Collen D. The plasminogen (fibrinolytic) system. Thromb Haemost 1999; 82: 259-70.
• 2 Collen D. Ham-Wasserman lecture: role of the plasminogen system in fibrin-homeostasis and tissue remodeling.. Hematology (Am Soc Hematol Educ Program) 2001; 1-9
• 3 Carmeliet P et al. Physiological consequences of loss of plasminogen activator gene function in mice. Nature 1994; 368: 419-24.
• 4 Siao CJ, Tsirka SE. Tissue plasminogen activator mediates microglial activation via its finger domain through annexin II. J Neurosci 2002; 22: 3352-8.
• 5 Hajjar KA, Jacovina AT, Chacko J. An endothelial cell receptor for plasminogen/tissue plasminogen activator. I. Identity with annexin II. J Biol Chem 1994; 269: 21191-7.
• 6 Qian Z et al. Tissue-plasminogen activator is induced as an immediate-early gene during seizure, kindling and long-term potentiation. Nature 1993; 361: 453-7.
• 7 Seeds NW, Williams BL, Bickford PC. Tissue plasminogen activator induction in Purkinje neurons after cerebellar motor learning. Science 1995; 270: 1992-4.
• 8 Seeds NW. et al. Neuronal migration is retarded in mice lacking the tissue plasminogen activator gene. Proc Natl Acad Sci U S A 1999; 96: 14118-23.
• 9 Salles FJ, Strickland S. Localization and regulation of the tissue plasminogen activator-plasmin system in the hippocampus. J Neurosci 2002; 22: 2125-34.
• 10 Pawlak R. et al. Tissue plasminogen activator in the amygdala is critical for stress-induced anxiety-like behavior. Nat Neurosci 2003; 6: 168-74.
• 11 Seeds NW. et al. Absence of tissue plasminogen activator gene or activity impairs mouse cerebellar motor learning. J Neurosci 2003; 23: 7368-75.
• 12 Rodrigues SM, Schafe GE, LeDoux JE. Molecular mechanisms underlying emotional learning and memory in the lateral amygdale. Neuron 2004; 44: 75-91.
• 13 Teesalu T. et al. Tissue plasminogen activator and neuroserpin are widely expressed in the human central nervous system. Thromb Haemost 2004; 92: 358-68.
• 14 Masos T, Miskin R. mRNAs encoding urokinasetype plasminogen activator and plasminogen activator inhibitor-1 are elevated in the mouse brain following kainate-mediated excitation. Brain Res Mol Brain Res 1997; 47: 157-69.
• 15 Yepes M, Lawrence DA. New functions for an old enzyme: nonhemostatic roles for tissue-type plasminogen activator in the central nervous system. Exp Biol Med 2004; 229: 1097-104.
• 16 Shin CY, Kundel M, Wells DG. Rapid, activity-induced increase in tissue plasminogen activator is mediated by metabotropic glutamate receptor-dependent mRNA translation. J Neurosci 2004; 24: 9425-33.
• 17 Zhuo M. et al. Role of tissue plasminogen activator receptor LRP in hippocampal long-term potentiation. J Neurosci 2000; 20: 542-9.
• 18 Pittman RN. Release of plasminogen activator and a calcium-dependent metalloprotease from cultured sympathetic and sensory neurons. Dev Biol 1985; 110: 91-101.
• 19 Gualandris A. et al. Membrane depolarization induces calcium-dependent secretion of tissue plasminogen activator. J Neurosci 1996; 16: 2220-5.
• 20 Parmer RJ. et al. 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 1997; 272: 1976-82.
• 21 Baranes D. et al. Tissue plasminogen activator contributes to the late phase of LTP and to synaptic growth in the hippocampal mossy fiber pathway. Neuron 1998; 21: 813-25.
• 22 Malenka RC, Nicoll RA. Long-term potentiation-- a decade of progress?. Science 1999; 285: 1870-4.
• 23 Pawlak R. et al. Rapid, specific and active site-catalyzed effect of tissue-plasminogen activator on hippocampus- dependent learning in mice. Neuroscience 2002; 113: 995-1001.
• 24 Pang PT. et al. Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science 2004; 306: 487-91.
• 25 Nicole O. et al. The proteolytic activity of tissueplasminogen activator enhances NMDA receptor-mediated signaling. Nat Med 2001; 7: 59-64.
• 26 Fernandez-Monreal M. et al. Arginine 260 of the amino-terminal domain of NR1 subunit is critical for tissue-type plasminogen activator-mediated enhancement of NMDA receptor signalling. J Biol Chem 2004; 279: 50850-6.
• 27 Matys T, Strickland S. Tissue plasminogen activator and NMDA receptor cleavage. Nat Med 2003; 9: 371-2. author reply 372–3.
• 28 Liu D. et al. Tissue plasminogen activator neurovascular toxicity is controlled by activated protein C. Nat Med 2004; 10: 1379-83.
• 29 Pawlak R. et al. From The Cover: Ethanol-withdrawal seizures are controlled by tissue plasminogen activator via modulation of NR2B-containing NMDA receptors. Proc Natl Acad Sci U S A 2005; 102: 443-8.
• 30 Wang X. et al. Lipoprotein receptor-mediated induction of matrix metalloproteinase by tissue plasminogen activator. Nat Med 2003; 9: 1313-7.
• 31 Yepes M. et al. Tissue-type plasminogen activator induces opening of the blood-brain barrier via the LDL receptor-related protein. J Clin Invest 2003; 112: 1533-40.
• 32 Madani R. et al. Enhanced hippocampal long-term potentiation and learning by increased neuronal expression of tissue-type plasminogen activator in transgenic mice. EMBO J 1999; 18: 3007-12.
• 33 Wolfer DP. et al. Spatial memory and learning in transgenic mice: fact or artifact?. News Physiol Sci 1998; 13: 118-23.
• 34 Matys T. et al. Tissue plasminogen activator promotes the effects of corticotropin-releasing factor on the amygdala and anxiety-like behavior. Proc Natl Acad Sci U S A 2004; 101: 16345-50.
• 35 Mataga N. et al. Enhancement of mRNA expression of tissue-type plasminogen activator by L-threo-3,4-dihydroxyphenylserine in association with ocular dominance plasticity. Neurosci Lett 1996; 218: 149-52.
• 36 Muller CM, Griesinger CB. Tissue plasminogen activator mediates reverse occlusion plasticity in visual cortex. Nat Neurosci 1998; 1: 47-53.
• 37 Mataga N, Nagai N, Hensch TK. Permissive proteolytic activity for visual cortical plasticity. Proc Natl Acad Sci U S A 2002; 99: 7717-21.
• 38 Mataga N. et al. Experience-dependent pruning of dendritic spines in visual cortex by tissue plasminogen activator. Neuron 2004; 44: 1031-41.
• 39 Oray S. et al. Dendritic spine dynamics are regulated by monocular deprivation and extracellular matrix degradation. Neuron 2004; 44: 1021-30.
• 40 Nagai T. et al. The tissue plasminogen activatorplasmin system participates in the rewarding effect of morphine by regulating dopamine release. Proc Natl Acad Sci U S A 2004; 101: 3650-5.
• 41 Tsirka SE. et al. Excitotoxin-induced neuronal degeneration and seizure are mediated by tissue plasminogen activator. Nature 1995; 377: 340-4.
• 42 Tsirka SE, Rogove AD, Strickland S. Neuronal cell death and tPA. Nature 1996; 384: 123-4.
• 43 Tsirka SE. et al. Neuronal death in the central nervous system demonstrates a non-fibrin substrate for plasmin. Proc Natl Acad Sci U S A 1997; 94: 9779-81.
• 44 Chen ZL, Strickland S. Neuronal death in the hippocampus is promoted by plasmin-catalyzed degradation of laminin. Cell 1997; 91: 917-25.
• 45 Indyk JA. et al. Laminin chain expression suggests that laminin-10 is a major isoform in the mouse hippocampus and is degraded by the tissue plasminogen activator/ plasmin protease cascade during excitotoxic injury. Neuroscience 2003; 116: 359-71.
• 46 Chen ZL, Indyk JA, Strickland S. The hippocampal laminin matrix is dynamic and critical for neuronal survival. Mol Biol Cell 2003; 14: 2665-76.
• 47 Nakagami Y. et al. Laminin degradation by plasmin regulates long-term potentiation. J Neurosci 2000; 20: 2003-10.
• 48 Yepes M. et al. Regulation of seizure spreading by neuroserpin and tissue-type plasminogen activator is plasminogen-independent. J Clin Invest 2002; 109: 1571-8.
• 49 Wang YF. et al. Tissue plasminogen activator (tPA) increases neuronal damage after focal cerebral ischemia in wild-type and tPA-deficient mice. Nat Med 1998; 4: 228-31.
• 50 Nagai N. et al. Role of plasminogen system components in focal cerebral ischemic infarction: a gene targeting and gene transfer study in mice. Circulation 1999; 99: 2440-4.
• 51 Yepes M. et al. Neuroserpin reduces cerebral infarct volume and protects neurons from ischemia-induced apoptosis. Blood 2000; 96: 569-76.
• 52 Cinelli P. et al. Neuroserpin, a neuroprotective factor in focal ischemic stroke. Mol Cell Neurosci 2001; 18: 443-57.
• 53 Selkoe DJ, Schenk D. Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol 2003; 43: 545-84.
• 54 Sutton R. et al. Plasminogen activator inhibitor-1 in the cerebrospinal fluid as an index of neurological disease. Blood Coagul Fibrinolysis 1994; 5: 167-71.
• 55 Mari D. et al. Hemostasis abnormalities in patients with vascular dementia and Alzheimer's disease. Thromb Haemost 1996; 75: 216-8.
• 56 Melchor JP, Pawlak R, Strickland S. The tissue plasminogen activator-plasminogen proteolytic cascade accelerates amyloid-beta (Abeta) degradation and inhibits Abeta-induced neurodegeneration. J Neurosci 2003; 23: 8867-71.
• 57 Van Nostrand WE, Porter M. Plasmin cleavage of the amyloid beta-protein: alteration of secondary structure and stimulation of tissue plasminogen activator activity. Biochemistry 1999; 38: 11570-6.
• 58 Tucker HM. et al. The plasmin system is induced by and degrades amyloid-beta aggregates. J Neurosci 2000; 20: 3937-46.
• 59 Tucker HM. et al. Tissue plasminogen activator requires plasminogen to modulate amyloid-beta neurotoxicity and deposition. J Neurochem 2000; 75: 2172-7.
• 60 Ledesma MD. et al. Brain plasmin enhances APP α -cleavage and A β degradation and is reduced in Alzheimer's disease brains. EMBO Rep 2000; 1: 530-5.
• 61 Ledesma MD. et al. Raft disorganization leads to reduced plasmin activity in Alzheimer's disease brains. EMBO Rep 2003; 4: 1190-6.
• 62 Madani R. et al. Impaired explorative behavior and neophobia in genetically modified mice lacking or overexpressing the extracellular serine protease inhibitor neuroserpin. Mol Cell Neurosci 2003; 23: 473-94.
• 63 Madani R, Nef S, Vassalli JD. Emotions are building up in the field of extracellular proteolysis. Trends Mol Med 2003; 9: 183-5.