Plasminogen activation in multiple sclerosis and other neurological disorders

Akenami, F.O.T.; Koskiniemi, M.; Vaheri, Antti

doi:10.1054/fipr.2000.0056

Cited by 6 publications

(4 citation statements)

References 133 publications

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“…3). The lower plasminogen level and tPA level in the MS patients are in line with the earlier findings [1,16], however, there is no exact explanation for such changes. We can make several suggestions: firstly, plasminogen from plasma might diffuse across a damaged BBB into brain parenchyma; secondly, plasma plasminogen could be converted to its active form, plasmin, and involved into the formation plasmin-α2-antiplasmin complexes.…”

Section: Discussionsupporting

confidence: 83%

Coagulation and Anticoagulation Parameters in Multiple Sclerosis Patients With and Without Covid-19

Halenova,

Raksha,

Vovk

et al. 2024

Clin. and prev. med.

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The aim. To investigate plasma levels of main coagulation and fibrinolytic factors in MS patients with and without COVID-19 history. Materials and methods. A total of 127 participants were enrolled in this study, including 97 MS patients and 30 healthy controls (HC). Patients with MS were divided into two groups: MS+Covid group (n=41) – patients with MS, who had a laboratory-verified diagnosis of COVID-19 in the past 3-6-month period and MS group (n=56) – patients with MS, who did not suffer from COVID-19 previously. Determination of plasma levels of prothrombin, plasminogen, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), protein C (PC), soluble thrombomodulin (TM) was performed by means of enzyme-linked immunosorbent assay. Spectrophotometric techniques were used to determine concentrations of fibrinogen, soluble fibrin monomeric complexes (SFMC) as well as plasminogen activity and inhibitory potential of α-2-antiplasmin. Results. The MS group was characterized by elevated levels of plasma prothrombin, fibrinogen, D-dimer, SFMC, soluble TM compared to HC, while PC concentration did not differ between MS and HC groups. Plasma plasminogen level as well as plasma level of the potential plasmin activity were significantly decreased in MS patients compared to HC group. The plasma tPA level was significantly reduced while plasma PAI-I level was significantly increased in MS patients compared to HC. Patients of MS group had an increased level of plasma α-2-antiplasmin activity compared with HC group. To note, most of studied parameters did not differ between two MS groups, except protein C, soluble thrombomodulin levels and plasma α-2-antiplasmin activity. Conclusions. The results of our study showed that MS patients have got altered hemostasis parameters; however, further study is necessary to find out the relationship between particular components of coagulation and fibrinolytic systems and pathophysiology of MS. Additionally, our findings demonstrated that a SARS-CoV-2 infection had a limited effect on hemostasis parameters in MS patients, causing changes in only a few parameters, including thrombomodulin and protein C levels as well as α-2-antiplasmin activity.

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Section: Discussionsupporting

confidence: 83%

Coagulation and Anticoagulation Parameters in Multiple Sclerosis Patients With and Without Covid-19

Halenova,

Raksha,

Vovk

et al. 2024

Clin. and prev. med.

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“…Although activation of serine proteases is considered essential to leukocyte entry and demyelination in inflammatory CNS lesions [10][11][12][13][14][15][16][17][18], acute relapses may result from a decrease of serpin concentrations. On the other hand, Akenami et al [11,14] described a normal serpine capacity in MS CSF, but findings concerning different serpins are still controversial [11,19]. Further studies on the regulation of individual serpins and their correlation with the development of MS lesions are needed.…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal fluid proteome profile in multiple sclerosis

et al. 2007

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Cerebrospinal fluid (CSF) proteins may provide important information about the pathomechanisms present in multiple sclerosis (MS). Although diagnostic criteria for early MS are available, there is still a need for biomarkers, predicting disease subtype and progression to improve individually tailored treatment. Using the two-dimensional difference gel electrophoresis (2-D-DIGE) technology for comparative analysis, we compared CSF samples from patients with MS of the relapse-remitting type (RRMS, n = 12) and from patients with clinically isolated syndrome (CIS, n = 12) suggestive of a first demyelinating attack with neurologically normal controls. Protein spots that showed more than two-fold difference between patients and controls were selected for further analysis with MALDI-TOF mass spectrometry. Immunoblot analysis was performed to confirm the validity of individual candidate proteins. In RRMS, we identified 1 up-regulated and 10 down-regulated proteins. In CIS, 2 up-regulated and 11 down-regulated proteins were identified. One of these proteins (Apolipoprotein A1) was confirmed by immunoblot. Though the pathophysiological role of these proteins still remains to be elucidated in detail and further validation is needed, these findings may have a relevant impact on the identification of disease-specific markers.

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“…The decrease in concentration in the plaque contraindicates a major role for tPA in the transmigration of inflammatory cells, but through activation by ECM proteins it may damage the blood–brain barrier, with leakage to the CSF. A specific tPA increase in the CSF of patients in relapse is well documented (Akenami et al, 2000). Localization of tPA in a subset of damaged axons with nonphosphorylated neurofilaments indicates a role in axonal damage.…”

Section: The Pa‐mmp Cascade In the Inflammatory Demyelinating Diseasementioning

confidence: 97%

Extracellular proteolysis in brain injury and inflammation: Role for plasminogen activators and matrix metalloproteinases

Wang

Cuzner

2002

J of Neuroscience Research

297

211

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The role of intracellular proteases (e.g., calpains and caspases) in the pathophysiology of neuronal cell death has been extensively investigated. More recently, accumulating data have suggested that extracellular proteolysis also plays a critical role. The two major systems that modify the extracellular matrix in brain are the plasminogen activator (PA) and matrix metalloproteinase (MMP) axes. This Mini-Review delineates major pathways of PA and MMP action after stroke, brain trauma, and chronic inflammation. Deleterious effects include the disruption of blood-brain barrier integrity, amplification of inflammatory infiltrates, demyelination, and possibly interruption of cell-cell and cell-matrix interactions that may trigger cell death. In contrast, PA-MMP actions may contribute to extracellular proteolysis that mediates parenchymal and angiogenic recovery after brain injury. As the mechanisms of deleterious vs. potentially beneficial PA and MMP actions become better defined, it is hoped that new therapeutic targets will emerge for ameliorating the sequelae of brain injury and inflammation.

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Plasminogen activation in multiple sclerosis and other neurological disorders

Cited by 6 publications

References 133 publications

Coagulation and Anticoagulation Parameters in Multiple Sclerosis Patients With and Without Covid-19

Coagulation and Anticoagulation Parameters in Multiple Sclerosis Patients With and Without Covid-19

Cerebrospinal fluid proteome profile in multiple sclerosis

Extracellular proteolysis in brain injury and inflammation: Role for plasminogen activators and matrix metalloproteinases

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