Fibrinolysis and Proteolysis最新文献

{"title":"Molecular transport during fibrin clot lysis","authors":"D.C. Rijken,&nbsp;D.V. Sakharov","doi":"10.1054/fipr.2000.0072","DOIUrl":"https://doi.org/10.1054/fipr.2000.0072","url":null,"abstract":"<div><p>Fibrin clot lysis is a dynamic process in which transport of fibrinolytic proteins plays an important role. Various recently established transport processes for plasminogen as well as for tissue-type and urokinase-type plasminogen activator (t-PA and u-PA, respectively) are reviewed.</p><p>During internal lysis of a plasma clot, plasminogen is translocated from the fluid phase to the surface of the lysing fibrin fibres. During external lysis, plasminogen strongly accumulates on the moving surface of the clot. In both types of lysis, binding takes place on C-terminal lysine residues in partially degraded fibrin that are generated by plasmin. The recently discovered thrombin activatable fibrinolysis inhibitor (TAFI) inhibits plasminogen binding by removing the C-terminal lysine residues. TAFI is a plasma carboxypeptidase B that is activated by thrombin and that links the coagulation system and the fibrinolytic system.</p><p>Transport of plasminogen activators is, in particular, essential for external clot lysis as it occurs during thrombolytic therapy. Because transport of proteins is not only mediated by diffusion, but also by fluid permeation, flow strongly promotes clot lysis. Penetration of plasminogen activators into clots is hampered by fibrin binding. While t-PA sticks to the surface of a clot, u-PA is able to enter a clot unhindered.</p><p>Recent studies show that ultrasound promotes plasminogen activator-induced clot lysis. A variety of mechanisms have been proposed to explain this promotion. Results indicate that an increased transport of fibrinolytic proteins significantly contributes to the acceleration of fibrinolysis by ultrasound.</p></div>","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"14 2","pages":"Pages 98-113"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0072","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71825680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of the expression, assembly, secretion and intracellular degradation of fibrinogen","authors":"C.M. Redman,&nbsp;H. Xia","doi":"10.1054/fipr.2000.0069","DOIUrl":"https://doi.org/10.1054/fipr.2000.0069","url":null,"abstract":"<div><p>The expression, assembly and secretion of fibrinogen are reviewed. Fibrinogen, the product of three exquisitely controlled genes, has a high basal level of expression and its production is further greatly increased in response to infection and/or tissue damage. In hepatocytes, the principal source of plasma fibrinogen, constitutive expression of the Aα and Bβ genes is mostly dependent on HNF-1 while the γ gene depends on at least three ubiquitous transcription factors. As a member of the acute phase proteins, fibrinogen expression is up-regulated by interleukin-6 (IL-6) and the glucocorticoids causing a coordinated expression of all three genes. IL-6 up-regulation of the fibrinogen genes involves activation of the STAT-3 and C/EBP transcription factors. Fibrinogen chain assembly occurs in the endoplasmic reticulum (ER) in a step-wise manner in which single chains form two-chain complexes (Aα-γ and Bβ-γ) which subsequently acquire a third chain to form a half-molecule. In a final step the two half-molecules are joined to form fibrinogen. Chain assembly is facilitated by chaperones and distinct structural domains of fibrinogen are necessary for proper assembly. Removal of the C-terminal half of the coiled coil region of the chains prevents chain assembly and disruption of the disulfide rings that flank the proximal N-terminal portion of the coiled-coil, or deletion of the N-terminal half of the coiled-coil, prevents half-molecules from forming dimers. Intracellular proteolysis plays a role in the regulation of fibrinogen chain assembly. Hepatocytes contain surplus Aα and γ chains and the ubiquitin-proteasome pathway is involved in degrading unassembled Bβ and γ chains. Aα-γ complexes are degraded by lysosomes.</p></div>","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"14 2","pages":"Pages 198-205"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0069","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71826158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent developments in thrombolytic therapy","authors":"D. Collen,&nbsp;H.R. Lijnen","doi":"10.1054/fipr.2000.0070","DOIUrl":"https://doi.org/10.1054/fipr.2000.0070","url":null,"abstract":"<div><p>One approach to the treatment of thrombosis consists of infusing thrombolytic agents to dissolve the blood clot and to restore tissue perfusion and oxygenation. Thrombolytic agents are plasminogen activators which activate the blood fibrinolytic system by activation of the proenzyme, plasminogen, to the active enzyme plasmin. Plasmin in turn digests fibrin to soluble degradation products. Inhibition of the fibrinolytic system occurs both at the level of the plasminogen activators, by plasminogen activator inhibitors, and at the level of plasmin, mainly by α₂-antiplasmin. Streptokinase, anisoylated plasminogen streptokinase activator complex (APSAC) and two-chain urokinase-type plasminogen activator (tcu-PA) induce extensive systemic plasmin generation; α₂-antiplasmin inhibits circulating plasmin but may become exhausted during thrombolytic therapy, since its plasma concentration is only about half that of plasminogen. As a result plasmin, which has a broad substrate specificity, will degrade several plasma proteins, such as fibrinogen, coagulation factors V, VIII and XII, and von Willebrand factor. These thrombolytic agents are, therefore, considered to be non-fibrin-specific. In contrast, the physiologic plasminogen activators, tissue-type plasminogen activator (t-PA) and single-chain u-PA (scu-PA), as well as the bacterial plasminogen activator staphylokinase, are more fibrin-specific because they activate plasminogen preferentially at the fibrin surface and less in the circulation, albeit via different mechanisms. Plasmin, associated with the fibrin surface, is protected from rapid inhibition by α₂-antiplasmin because its lysine-binding sites are not available, and may thus efficiently degrade the fibrin of a thrombus. Several mutants and variants, mainly of fibrin-specific plasminogen activators, are being evaluated in clinical trials in patients with acute myocardial infarction.</p></div>","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"14 2","pages":"Pages 66-72"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71826159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular interactions between the plasminogen/plasmin and matrix metalloproteinase systems","authors":"H. Lijnen","doi":"10.1054/FIPR.2000.0065","DOIUrl":"https://doi.org/10.1054/FIPR.2000.0065","url":null,"abstract":"Abstract Circumstantial evidence suggests an important role of the fibrinolytic (plasminogen/plasmin) and matrix metalloproteinase (MMP) systems in biological processes involving (extra)cellular proteolysis and matrix degradation. The availability of mice with inactivation of main components of both systems has allowed to study directly the interactions between both systems and their biological role. In purified system, MMP-3 (stromelysin-1) specifically hydrolyzes plasminogen and urokinase-type plasminogen activator (u-PA), thereby removing the cellular binding domains from both proteins. In the presence of cells, MMP-3 may downregulate cell-associated plasmin activity by decreasing the amount of activatible plasminogen, without affecting cell-bound u-PA activity. During neointima formation after vascular injury in gene-deficient mice, expression of MMP-2 and MMP-9 (gelatinase A and B) is strongly enhanced, independently of the presence or absence of plasminogen or of the physiological plasminogen activators. Activation of proMMP-2 occurs independently of plasmin, whereas proMMP-9 activation occurs via plasmin-dependent as well as plasmin-independent mechanisms. The temporal and topographic expression patterns of MMP-2, MMP-3, MMP-9, MMP-12 (metalloelastase) and MMP-13 (collagenase) establish a potential role in neointima formation. This is further substantiated by the finding that neointima formation after vascular injury is significantly enhanced in mice with deficiency of TIMP-1, a main physiological MMP inhibitor. Atherosclerosis models in gene-deficient mice suggest an important role of u-PA in the structural integrity of the atherosclerotic vessel wall. u-PA-mediated plasmin generation may contribute to activation of latent MMPs (MMP-3, -9, -12, and -13) which degrade insoluble elastin and fibrillar collagen. Thus, studies with gene-deficient mice have allowed to establish novel interactions between the fibrinolytic and MMP systems, which may play a role in biological processes requiring cellular proteolytic activity and/or extracellular matrix degradation.","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"55 1","pages":"175-181"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82627234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor cell-mediated proteolysis: regulatory mechanisms and functional consequences","authors":"Supurna Ghosh, S. Ellerbroek, Yi I. Wu, M. Stack","doi":"10.1054/FIPR.2000.0060","DOIUrl":"https://doi.org/10.1054/FIPR.2000.0060","url":null,"abstract":"Abstract The mammalian organism is composed of an inter-dependent series of tissue compartments separated from each other by an extracellular matrix (ECM). This ECM functions as both a determinant of tissue architecture and a mechanical barrier to cellular invasion. ECM proteolysis facilitates tissue penetration, and a distinctive property of many malignant tumor cells is the capacity to invade host tissues and establish metastatic foci. Malignant cells produce a spectrum of matrix-degrading proteinases with activities directed against the major ECM proteins. These enzymes are identical to those normally involved in physiologic processes; however, proteinase regulation is altered such that enzyme expression and/or activity are inappropriately controlled. The purpose of this review is to highlight biochemical mechanisms commonly utilized by tumor cells to regulate proteinase activity and to discuss the potential functional consequences with respect to tumor cell behavior. Specific examples will be provided to illustrate the concepts of regulation via limited proteolysis, enzyme-inhibitor binding, compartmentalization, and alteration of proteinase expression.","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"34 1","pages":"87-97"},"PeriodicalIF":0.0,"publicationDate":"2000-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81028377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the interaction of plasminogen activator inhibitor type 1 with vitronectin by surface plasmon resonance","authors":"J. Ehnebom ,&nbsp;P. Björquist ,&nbsp;O. Sigurdardottir ,&nbsp;J. Deinum","doi":"10.1054/fipr.2000.0052","DOIUrl":"https://doi.org/10.1054/fipr.2000.0052","url":null,"abstract":"Abstract In plasma all plasminogen activator inhibitor type 1 (PAI-1) is found in complex with vitronectin (VN). We have investigated the interaction of human PAI-1 with monomeric native human VN by size exclusion chromatography with VN in solution and using the surface plasmon resonance technique (SPR) with immobilised VN. With these techniques PAI-1 is found to bind in a tight one-to-one complex. VN in solution competed with amine coupled VN in binding free active PAI-1 with a K D of 20 nM. A K D of 0.1 nM at 25°C was instead found for PAI-1 binding to immobilised VN. The extremely rapid binding of PAI-1 to immobilised VN had an association rate constant, κ on of 20 μ M –1 s –1 . By the immobilisation of VN the affinity for PAI-1 thus increased manifold. The stable substrate mutant PAI-1-Ala335Glu had similar binding characteristics for immobilised VN as active PAI-1. Upon injection of human α-thrombin onto PAI-1 captured on VN the ternary complex was formed and PAI-1 rapidly dissociated from immobilised VN, indicating that VN was not converted into the denatured form by amine coupling. Monoclonal antibodies against PAI-1, belonging to five different classes did all bind to PAI-1 captured on immobilised VN. There is thus no direct overlap of either of these five antibody binding epitopes on PAI-1 with the binding site for VN. PAI-1 was released from immobilised VN by addition of tissue plasminogen activator (tPA) (E.C. 3.4.21.68), with a dissociation rate depending on the tPA concentration. The preformed complex of tPA and PAI-1 did not bind to immobilised VN. An intermediate ternary complex with tPA and active PAI-1 captured on VN is not detected with SPR. On the contrary, a transient ternary complex was observed with tPA and PAI-1-Ala335Glu captured on VN. In conclusion, these results reject that VN is bound to any of the five antibody binding epitopes, and support the proposal that the binding surface for VN on PAI-1 is located near the epitope of tPA in the final complex, including parts of α-helices C, E and β-strand 1A.","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"14 1","pages":"47-57"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71794370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A peptide ligand of the human thrombin receptor antagonizes thrombin receptor activating peptide and α -thrombin-induced platelet aggregation","authors":"R. Pakala ,&nbsp;T.Chyou Liang ,&nbsp;C.R. Benedict","doi":"10.1054/fipr.2000.0046","DOIUrl":"https://doi.org/10.1054/fipr.2000.0046","url":null,"abstract":"Abstract Structure and function studies on thrombin receptor activating peptide have revealed that certain residues in this peptide could be replaced with alanine. Attempts to prepare antagonist peptides by single amino acid modification of thrombin receptor activating peptide have not resulted in potent antagonist peptide. In the present study, we report an antagonist peptide with multiple alanine substitutions in both critical and non-critical residues. At a concentration of 32 μM, this peptide could completely block agonist-induced platelet aggregation. The magnitude of the antagonist effect of this peptide depends on the concentration of the antagonist and preincubation time. This peptide blocked the platelet aggregation induced by the agonist peptide and also by α-thrombin, but did not have any effect on adenosine diphosphate or collagen-induced platelet aggregation indicating that the antagonist affects of this peptide may be pertained to thrombin receptor mediated events only. This peptide may be useful for blocking thrombin-mediated events like thrombosis and restenosis or can be used as a template for developing more efficient thrombin receptor antagonists.","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"14 1","pages":"15-21"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71794497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of a complex between active plasminogen activator inhibitor-1 and N-terminal fragments of vitronectin from human placenta","authors":"M. Philips,&nbsp;A.H. Johnsen,&nbsp;S. Thorsen","doi":"10.1054/fipr.2000.0047","DOIUrl":"https://doi.org/10.1054/fipr.2000.0047","url":null,"abstract":"Abstract Two different forms of active plasminogen activator inhibitor-1 (PAI-1) were purified from human placenta and characterized. One form with Mr>230 000 was identical to the complex between PAI-1 and multimeric vitronectin in plasma as evidenced by gel filtration and immunological analysis. The other form was a complex between PAI-1 and N-terminal fragments of vitronectin as demonstrated by a combination of amino acid sequence analysis and mass spectrometry of polypeptides obtained from the purified complex after reverse phase high pressure liquid chromatography (HPLC). The vitronectin fragments were 42 to 67 amino acids long, the dominant fragment being residues 1–49. This fragment of vitronectin encompasses the binding sites for both PAI-1, the urokinase receptor (uPAR) and integrins. Consistent with the primary binding site for PAI-1 being localized to the N-terminal domain of vitronectin, the complex between PAI-1 and N-terminal vitronectin fragments did not bind intact vitronectin. PAI-1 bound to N-terminal vitronectin fragments or to multimeric vitronectin showed the same functional stability and comparable second order rate constants for the inhibition of single-chain tissue-type plasminogen activator (tPA). The proteolytic cleavages producing the complex between PAI-1 and N-terminal vitronectin fragments may take place in vivo and lead to modulation of thrombotic and tissue remodelling processes.","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"14 1","pages":"22-34"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71794498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Presence of tissue plasminogen activator (t-PA) in the adventitial sympathetic nerves that innervate small arteries: morphologic evidence for a neural fibrinolysis","authors":"X. Jiang ,&nbsp;Y. Wang ,&nbsp;A.R. Hand ,&nbsp;C. Gillies ,&nbsp;R.E. Cone ,&nbsp;J. JO’Rourke","doi":"10.1054/fipr.2000.0048","DOIUrl":"https://doi.org/10.1054/fipr.2000.0048","url":null,"abstract":"Abstract Objective : Previous functional studies have indicated that: (i) sympathetic neurons synthesize, store and release tissue plasminogen activator (t-PA); (ii) small, densely innervated arteries release more t-PA than large sparsely innervated ones; and (iii) sympathectomy greatly reduces arterial t-PA release. This study was done to provide morphologic evidence of the existence of a non-endothelial fibrinolytic system within the adventitial nerve plexus of small arteries and arterioles. Methods : t-PA and neuropeptide Y (NPY) localizations in the adventitial nerve fibers of small and large arteries were examined. Whole mount preparations were used to emphasize immunostaining of the adventitial plexus and the iris. Using confocal and electron microscopy, t-PA was also immunolocalized in isolated sympathetic neurons and the axons of small arteries. The previous comparative t-PA release from cultured small and large artery explants was re-examined. Results : Small arteries – surface views of the mesenteric adventitia showed confinement of t-PA to a dense plexus of NPY-positive sympathetic nerve fibers. Cryosections confirmed the presence within a multilayered plexus at the smooth muscle interface, and in the endothelial monolayer. Comparatively, sections of arterioles showed a heavier layer of NPY- and t-PA-positive material that occupied most of the wall thickness. Electron microscopic views confirmed the discrete confinement of non-endothelial t-PA within the mesenteric artery adventitial plexus. In control plexus immunostainings of the iris, t-PA was largely confined to the densely innervated dilator muscle. Large arteries – surface views of the carotid and aortic adventitia showed a sparse presence of thin NPY and t-PA positive lines that followed the contours of vasa vasora walls, within which endothelial and nerve fiber t-PA could not be separately identified. Cryosections of the carotid and aorta adventitia also showed a sparse NPY and t-PA staining limited to isolated arterioles and axons. Endothelial t-PA immunostaining in carotid and aorta whole mount sections was scant. Neurons – t-PA immunostaining of most sympathetic ganglion neurons was positive. Confocal images of isolated sympathetic neurons revealed the storage of immunoreactive t-PA in closely packed secretory granules within the cell body and axons. Conclusions : • The adventitial sympathetic nerve plexus contains the major portion of the immunoreactive t-PA that is stored in small artery walls. • Like norepinephrine t-PA is transported and stored in secretory granules within the sympathetic axons that preferentially innervate small arteries. • The content and release of t-PA from artery walls appears inversely proportional to vessel diameter, and directly proportional to innervation density. These findings are consistent with the hypothesis that t-PA is supplied to resistance arteries and arterioles by the sympathetic nervous system.","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"14 1","pages":"35-46"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71794371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasminogen activation in multiple sclerosis and other neurological disorders","authors":"F.O.T. Akenami,&nbsp;M. Koskiniemi,&nbsp;A. Vaheri","doi":"10.1054/fipr.2000.0056","DOIUrl":"https://doi.org/10.1054/fipr.2000.0056","url":null,"abstract":"Abstract Recent studies have implicated tissue-type plasminogen activator (tPA) in neurodegenerative conditions. A role in synaptic remodelling has been suggested for tPA, since elevated mRNA and protein levels were detected in the neuronal cells of mice trained to negotiate a pegged runway. tPA has also been implicated in the failure of neuronal survival in the presence of excitotoxic challenge. Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) of largely unknown aetiology, affecting young and middle-aged adults. The myelin sheaths surrounding nerves in the brain and spinal cord are damaged, which affects the function of the nerves involved. The disease affects different parts of the brain and spinal cord, resulting in typically scattered symptoms. Elevated activities of cerebrospinal fluid (CSF) tPA have been found in neurological patients when compared with reference subjects: MS > leukaemia > encephalitis. The PAI-1 levels were the reverse of tPA activities: leukaemia > encephalitis > MS. Samples with quantifiable CSF uPA levels also had high levels of PAI-1 in the same order: leukaemia > encephalitis > MS, both for uPA and PAI-1. Reduced plasminogen concentrations and plasmin-α2-antiplasmin (PAP) complexes have been found in the CSF of MS patients. In MS brain, an increased expression of tPA mRNA and protein in neurons, mononuclear cells within perivascular cuffs, and foamy macrophages in demyelinating plaques, have been found. While normal tPA levels may be of physiological benefit to the brain and in selected conditions even therapeutic, exaggerated levels may result in tissue damage. This review covers current knowledge of MS, and plasminogen activation in MS and some neurological disorders such as encephalitis and leukaemia.","PeriodicalId":100526,"journal":{"name":"Fibrinolysis and Proteolysis","volume":"14 1","pages":"1-14"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1054/fipr.2000.0056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71794496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}