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The role of the Plasminogen activating system in Neurobiology

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The plasminogen activating system is well known for its capacity to remove fibrin and to break down blood clots and was harnessed for clinical use in patients with myocardial infarction and ischaemic stroke. However in recent years, this enzyme system has been found to play unsuspected, yet important roles in ...

The plasminogen activating system is well known for its capacity to remove fibrin and to break down blood clots and was harnessed for clinical use in patients with myocardial infarction and ischaemic stroke. However in recent years, this enzyme system has been found to play unsuspected, yet important roles in the central nervous system. Initial reports indicated a role for this system in the promotion of synaptic plasticity and memory formation, while subsequent studies revealed that this system could engage glutamate receptors, enhance calcium influx and promote neurotoxicity. In models of ischaemic stroke and traumatic brain injury, the plasminogen activating system has been shown to modulate blood brain barrier permeability which has important clinical implications, particularly in ischaemic stroke given that tissue-type plasminogen activator (t-PA), is still the only approved thrombolytic drug in this condition. Recent reports have also provided evidence for a neuroprotective role for t-PA is some models of cerebral ischaemia. While this has initiated much controversy in this field, more recent reports have provided compelling evidence to implicate t-PA and related proteases in the promotion of neurodegenerative disorders, including Alzheimer’s disease and in ataxia. This is a vibrant field that is likely to generate intense research over the next decade. We therefore propose to host a Frontiers Research Topic that covers the growing interest of the plasminogen activating system in the brain, with particular focus on ischaemic stroke, traumatic brain injury, blood brain barrier permeability and in neurodegenerative conditions.


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