The plasminogen activation system in neuroinflammation.
The plasminogen activation (PA) system consists in a group of proteases and protease inhibitors regulating the activation of the zymogen plasminogen into its proteolytically active form, plasmin. Here, we give an update of the current knowledge about the role of the PA system on different aspects of neuroinflammation. These include modification in blood-brain barrier integrity, leukocyte diapedesis, removal of fibrin deposits in nervous tissues, microglial activation and neutrophil functions. Furthermore, we focus on the molecular mechanisms (some of them independent of plasmin generation and even of proteolysis) and target receptors responsible for these effects. The description of these mechanisms of action may help designing new therapeutic strategies targeting the expression, activity and molecular mediators of the PA system in neurological disorders involving neuroinflammatory processes. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger.
INSERM, INSERM-U919 "serine proteases and pathophysiology of the neurovascular unit", Université de Caen Basse-Normandie, Caen, France, GIP Cyceron, Caen, France.
Anupriya
A
Mehra
INSERM, INSERM-U919 "serine proteases and pathophysiology of the neurovascular unit", Université de Caen Basse-Normandie, Caen, France, GIP Cyceron, Caen, France.
Carine
C
Ali
INSERM, INSERM-U919 "serine proteases and pathophysiology of the neurovascular unit", Université de Caen Basse-Normandie, Caen, France, GIP Cyceron, Caen, France.
Jérôme
J
Parcq
INSERM, INSERM-U919 "serine proteases and pathophysiology of the neurovascular unit", Université de Caen Basse-Normandie, Caen, France, GIP Cyceron, Caen, France.
Denis
D
Vivien
INSERM, INSERM-U919 "serine proteases and pathophysiology of the neurovascular unit", Université de Caen Basse-Normandie, Caen, France, GIP Cyceron, Caen, France. Electronic address: docagne@cyceron.fr.
Fabian
F
Docagne
D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology* / Q000473:pathology; D002493:Central Nervous System Diseases / Q000276:immunology* / Q000473:pathology; D005337:Fibrin / Q000276:immunology; D005341:Fibrinolysin / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D017628:Microglia / Q000276:immunology* / Q000473:pathology; D010958:Plasminogen / Q000276:immunology*; D010959:Tissue Plasminogen Activator / Q000276:immunology
D005337:Fibrin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin
Blood-brain barrier; Leukocytes; Microglia; Plasminogen activator