Role of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in psychological stress and depression

Shih-Jen Tsai _

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Oncotarget. 2017; 8:113258-113268. https://doi.org/10.18632/oncotarget.19935

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Shih-Jen Tsai1,2

1Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan

2School of Medicine, National Yang-Ming University, Taipei, Taiwan

Correspondence to:

Shih-Jen Tsai, email: [email protected]

Keywords: brain-derived neurotrophic factor, tissue-type plasminogen activator, plasminogen activator inhibitor-1, major depressive disorder, stress

Received: May 30, 2017     Accepted: July 25, 2017     Published: August 04, 2017


Major depressive disorder is a common illness worldwide, but the pathogenesis of the disorder remains incompletely understood. The tissue-type plasminogen activator-plasminogen proteolytic cascade is highly expressed in the brain regions involved in mood regulation and neuroplasticity. Accumulating evidence from animal and human studies suggests that tissue-type plasminogen activator and its chief inhibitor, plasminogen activator inhibitor-1, are related to stress reaction and depression. Furthermore, the neurotrophic hypothesis of depression postulates that compromised neurotrophin brain-derived neurotrophic factor (BDNF) function is directly involved in the pathophysiology of depression. In the brain, the proteolytic cleavage of proBDNF, a BDNF precursor, to mature BDNF through plasmin represents one mechanism that can change the direction of BDNF action. We also discuss the implications of tissue-type plasminogen activator and plasminogen activator inhibitor-1 alterations as biomarkers for major depressive disorder. Using drugs that increase tissue-type plasminogen activator or decrease plasminogen activator inhibitor-1 levels may open new avenues to develop conceptually novel therapeutic strategies for depression treatment.

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