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The P11, tPA/plasminogen system and brain-derived neurotrophic factor: Implications for

Summary: The P11, tPA/plasminogen system and
brain-derived neurotrophic factor: Implications for
the pathogenesis of major depression and the
therapeutic mechanism of antidepressants
Shih-Jen Tsai *
Department of Psychiatry, Taipei Veterans General Hospital and Division of Psychiatry,
School of Medicine, National Yang-Ming University, No. 201 Shih-Pai Road, Sec. 2, 11217 Taipei, Taiwan
Received 28 May 2006; accepted 2 June 2006
Summary Major depressive disorder (MDD) is a common disabling psychiatric illness with an unknown etiology.
Evidence from animal and human studies suggests that a disturbance in serotonergic (5-HT) activity and/or brain-
derived neurotrophic factor (BDNF) signaling may be implicated in the pathogenesis of MDD. Recently, a protein, p11,
has been found to increase the number of 5-HT1B receptors on the surface of cells and enhance 5-HT1B receptor
function. Furthermore, mice over-expressing p11 acted as if they were undergoing treatment with antidepressants and
p11 knockout mice exhibit a depression-like phenotype and reduced behavioural reactions to an antidepressant. As
tissue-type plasminogen activator (tPA)/plasminogen proteolytic cascade is implicated in the cleavage of proBDNF to
BDNF, and p11, a component of the Annexin II, which can greatly enhance the activation of plasmin by tPA, it is
proposed that p11 may act through the tPA/plasminogen/BDNF pathway to achieve its antidepressant effect. Attempts
to confirm this hypothesis may lead to new directions in the study of the pathogenesis of MDD and the development of a
novel intervention for this disorder. In addition, BDNF is also implicated in several psychiatric diseases such as
schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder and Alzheimer's disease; whether p11 and


Source: Alford, Simon - Department of Biological Sciences, University of Illinois at Chicago


Collections: Biology and Medicine