Tissue-type plasminogen activator and neuroserpin: a well-balanced act in the nervous system?

Tissue-type plasmingen activator (tPA) is a highly specific serine proteinase that activates the zymogen plasminogen to the broad-specificity proteinase plasmin. tPA is found in the blood, where its primary function is as a thrombolytic enzyme, as well as in the central nervous system (CNS), where it promotes events associated with synaptic plasticity and cell death in a number of settings, such as cerebral ischemia and seizures. Neuroserpin is a fully inhibitory serine proteinase inhibitor (serpin) that reacts preferentially with tPA, and is located in regions of the brain where either tPA message or tPA protein are also found, suggesting that neuroserpin is the selective inhibitor of tPA in the CNS. There is a growing body of evidence demonstrating the participation of tPA in a number of physiologic and pathologic events in the CNS, and the role of neuroserpin as the natural regulator of tPA's activity in these processes.