title: The possible role of tissue-type plasminogen activator and the plasminogen system in the pathogenesis of major depression.
abstract: Major depressive disorder (MDD) is one of the most common psychiatric illnesses with an unknown etiology. Evidence from animal and human studies has suggested that brain-derived neurotrophic factor (BDNF) function may be implicated in the pathogenesis of MDD. Tissue-type plasminogen activator (tPA) is a highly specific serine proteinase that catalyses the generation of zymogen plasminogen from the proteinase plasmin. Recent studies have found that the proteolytic cleavage of proBDNF, a BDNF precursor, to BDNF by the plasmin represents a mechanism by which the direction of BDNF action is controlled. Furthermore, studies using mice deficient in tPA has demonstrated that tPA is important for the stress reaction, a common precipitating factor for MDD. A study of the serum levels of the plasminogen activator inhibitor-1 (PAI-1), the major inhibitor of tPA, found that women with MDD had a higher PAI-1 concentration than normal controls. From these findings, it is proposed that the tPA/plasminogen system may play a role in the pathogenesis of MDD. Attempts to confirm the tPA/plasminogen hypothesis may lead to new directions in the study of the pathogenesis of MDD and the development of a novel intervention of this disorder.
authors.affiliation: Department of Psychiatry, Taipei Veterans General Hospital, and Division of Psychiatry, School of Medicine, National Yang-Ming University, No. 201 Shih-Pai Road, Section 2, Taipei 11217, Taiwan. sjtsai@vghtpe.gov.tw
authors.forename: Shih-Jen
authors.initials: SJ
authors.lastname: Tsai
mesh_terms: D003865:Major Depressive Disorder / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D010958:Plasminogen / Q000502:physiology*; D010959:Tissue Plasminogen Activator / Q000502:physiology*
chemical_list: D010958:Plasminogen; D010959:Tissue Plasminogen Activator