Tissue plasminogen activator in the amygdala: a new role for an old protease

Evidence has accumulated that point to the tissue plasminogen activator (tPA), a serine protease historically associated with blood physiology, as an important regulator of the central nervous system functioning. tPA is highly expressed in the limbic system where it regulates neuronal viability and experience-induced plasticity. In the amygdala tPA is a critical mediator of stress-induced structural and functional rearrangements that ultimately shape up behavioral responses to stressful stimuli. The importance of tPA in the limbic system was confirmed using tPA-deficient mice; these animals do not show biochemical, structural and behavioral signatures normally associated with stress. tPA-mediated facilitation of experience-induced plasticity in the limbic system is mediated by a complex mechanism that may involve direct or indirect interactions of tPA with NMDA receptor, its binding to the LRP receptor or activation of brain-derived growth factor.