Tissue Plasminogen Activator Signaling in the Normal and Diseased Brain

Tissue-type plasminogen activator (tPA) is a protein whose enzymatic and nonenzymatic properties make it critical to normal and pathological events within the central nervous system. Here we outline the known roles of tPA in common proteolytic and hemolytic processes that underlie normal tissue functions as well as pathological events, particularly in the brain. Cerebral ischemia is a large global health concern as sharp increases in its occurrence are experienced by developed countries. Ischemic events stem from a lack of blood flow to neural tissues. tPA has long been implicated in potential excitotoxic and/or neuroprotectant events during cerebral ischemic injury, whether through extracellular events, such as the generation of plasmin and the effective clotting of blood, or intracellular events, such as membrane receptor activation. tPA has been shown to have a broad role in these processes leading to the postulate that this multifunctional molecule plays an essential role in brain homeostasis.