PLG and major depressive disorder: Thus, the proteolytic processing of proBDNF by the tPA/plasminogen system represents a powerful means of regulating the direction of BDNF action that in turn could be implicated in MDD pathogenesis and in the mechanism of action of antidepressant drugs.13, 16 However, very little is known about the role of the tPA–BDNF pathway in depression.